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Abstract Inhibition of the mitochondrial oxidative phosphorylation (OXPHOS) system can lead to metabolic disorders and neurodegenerative diseases. In primary mitochondrial disorders, reactive astrocytes often accompany neuronal degeneration and may contribute to neurotoxic inflammatory cascades that elicit brain lesions. The influence of mitochondria to astrocyte reactivity as well as the underlying molecular mechanisms remain elusive. Here we report that mitochondrial Complex I dysfunction promotes neural progenitor cell differentiation into astrocytes that are more responsive to neuroinflammatory stimuli. We show that the SWItch/Sucrose Non-Fermentable (SWI/SNF/BAF) chromatin remodeling complex takes part in the epigenetic regulation of astrocyte responsiveness, since its pharmacological inhibition abrogates the expression of inflammatory genes. Furthermore, we demonstrate that Complex I deficient human iPSC-derived astrocytes negatively influence neuronal physiology upon cytokine stimulation. Together, our data describe the SWI/SNF/BAF complex as a sensor of altered mitochondrial OXPHOS and a downstream epigenetic regulator of astrocyte-mediated neuroinflammation.

Functionalized porous silica materials were synthesized in alkaline conditions by post-grafting method using hexadecyltrimethylammonium bromide (CTAB) as templating agent, tetraethyl orthosilicate (TEOS) as silica precursors and trialkoxysilanes functionalised with different organic groups. Textural features, halfway between microporosity and mesoporosity, combined with the surface physico-chemical ones related to various organic groups, determined different CO2 storage properties highlighting a strong interaction with the precursor 3-Aminopropyl)triethoxysilane. NMR spectroscopy also showed how physisorption is the mainstream mechanism for CO2 adsorption in all the sorbents, except for the aforementioned organic group in which an important chemisorption contribution occurs. Diffusion and molecular mobility analysis revealed that at least two species coexist within the micro-/meso-pores of the sorbents, namely, CO2 molecules powerfully interacting with the pore surface (pore-surface CO2) and “bulk-like” CO2 filling the central region of the pores. Furthermore, the post functionalization suppresses the diffusion of CO2 molecules through the pore channels with all the functionalized materials exhibiting a single self-diffusion coefficient. On the other side, D// strictly depends on the average pore size of the sorbent.

Abstract Extending the operation of proton exchange membrane fuel cells (PEMFCs) at high temperature (i.e., 120 °C) and/or low relative humidity (

Chorea is a hyperkinetic movement disorder frequently observed in the pediatric population, and, due to advancements in genetic techniques, an increasing number of genes have been associated with this disorder. In genetic conditions, chorea may be the primary feature of the disorder, or be part of a more complex phenotype characterized by epileptic encephalopathy or a multisystemic syndrome. Moreover, it can appear as a persistent disorder (chronic chorea) or have an episodic course (paroxysmal chorea). Managing chorea in childhood presents challenges due to its varied clinical presentation, often involving a spectrum of hyperkinetic movement disorders alongside neuropsychiatric and multisystemic manifestations. Furthermore, during infancy and early childhood, transient motor phenomena resembling chorea occurring due to the rapid nervous system development during this period can complicate the diagnosis. This review aims to provide an overview of the main genetic causes of pediatric chorea that may manifest during infancy and early childhood, focusing on peculiarities that can aid in differential diagnosis among different phenotypes and discussing possible treatment options.

Abstract Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.

BackgroundAn estimated 57.4 million people live with dementia worldwide, with the social burden of the disease steadily growing. Despite the approval of lecanemab and ongoing trials, there is still a lack of effective and safe treatments for behavioral and psychological symptoms of dementia (BPSD), which affect 99% of patients. Agitation is one of the most disabling BPSD, with a cross-sectional prevalence of ≥50% in nursing homes, and refers to help-seeking behavior in response to various sources of discomfort, among which pain is a crucial component.MethodsThis pilot phase of the BRAINAID (NCT04321889) trial aimed to assess the effectiveness of the patented nanotechnological device NanoBEO in older (≥65 years) people with severe dementia. This randomized placebo-controlled trial, with quadruple masking that involved all operators and participants, followed the SPIRIT and CONSORT statements. A total of 29 patients completed the trial. The patients were randomly allocated in a 1:1 ratio to the NanoBEO or placebo group, and the corresponding product was applied on both arms once daily for 4 weeks, with a 4-week follow-up period. The primary endpoint was efficacy against agitation. The secondary endpoints were efficacy against agitation at follow-up and efficacy against pain. Any adverse events were reported, and biochemical analyses were performed.ResultsThe NanoBEO intervention reduced the frequency (28%) and level of disruptiveness of agitated behaviors. The effect on frequency was statistically significant after 2 weeks of treatment. The efficacy of NanoBEO on agitated behaviors lasted for the entire 4-week treatment period. No additional psychotropic drugs were prescribed throughout the study duration. The results after 1 week of treatment demonstrated that NanoBEO had statistically significant analgesic efficacy (45.46% improvement in pain intensity). The treatment was well tolerated.DiscussionThis trial investigated the efficacy of NanoBEO therapy in managing agitation and pain in dementia. No need for rescue medications was recorded, strengthening the efficacy of NanoBEO in prolonged therapy for advanced-stage dementia and the usefulness of the intervention in the deprescription of potentially harmful drugs. This study provided a robust rationale for the application of NanoBEO in a subsequent large-scale pivotal trial to allow clinical translation of the product.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT04321889.

Rhabditis (Rhabditella) axei is a free-living, pseudoparasitic, necromenic, and parasitic nematode, depending on the host. This species feeds mainly on bacteria present in decaying organic matter, soil, and other substrates; however, in its parasitic form, it can colonize some species of snails. Moreover, the presence of R. axei has also been detected in birds and mammals, including humans.

BackgroundSleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.MethodsA total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7–35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L’Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients’ contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated.ResultsOf the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03–82%)] and HR/LF [median: 3.75 (interquartile range 3.19–5.05)] were elevated, independent from the wake–sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.ConclusionOur findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.

Abstract The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG. PROSPERO registration: CRD42023434867.

Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

ABSTRACT: Aims: Myocardial inflammation is increasingly detected noninvasively by tissue mapping with cardiovascular magnetic resonance (CMR). Intraindividual agreement with endomyocardial biopsy (EMB) or markers of myocardial injury, high-sensitive cardiac troponin (hs-cTnT) in patients with clinically suspected viral myocarditis is incompletely understood. Methods: Prospective multicenter study of consecutive patients with clinically suspected myocarditis who underwent blood testing for hs-cTnT, CMR, and EMB as a part of diagnostic workup. EMB was considered positive based on immunohistological criteria in line with the European Society of Cardiology (ESC) definitions. CMR diagnoses employed tissue mapping using sequence-specific cut-off for native T1 and T2 mapping; active inflammation was defined as T1 ≥2 standard deviation (SD) and T2 ≥2 SD above the mean of normal range. Hs-cTnT of greater than 13.9 ng/L was considered significant. Results: A total of 114 patients (age (mean ± SD) 54 ± 16, 65% males) were included, of which 79 (69%) had positive EMB criteria, 64 (56%) CMR criteria, and a total of 58 (51%) positive troponin. Agreement between EMB and CMR diagnostic criteria was poor (CMR vs ESC: area under the curve (AUC): 0.51 (0.39–0.62)). The agreement between a significant hs-cTnT rise and CMR-based diagnosis of myocarditis was good (AUC: 0.84 (0.68–0.92); p

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring’s neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.

Background: The CONtrolled delivery For ImproveD outcomEs with cliNiCal Evidence registry was initiated to characterize the clinical safety and device performance from experienced transcatheter aortic valve implantation (TAVI) centers in Europe and Australia that use the Portico valve to treat patients with severe aortic stenosis. We herein report for the first time the valve performance at 30-day across all implanted valve sizes and the 1-year survival from this registry. Methods: This was a prospective, multicenter, single-arm observational clinical investigation of patients clinically indicated for implantation of a Portico valve in experienced TAVI centers. Patients were treated with a commercially available valve (size 23, 25, 27, or 29 mm) using either the first-generation delivery system (DS) (n = 501) or the second-generation (FlexNav) DS (n = 500). Adverse events were adjudicated by an independent clinical events committee according to Valve Academic Research Consortium-2 criteria. Echocardiographic outcomes were assessed at 30 days by an independent core laboratory, and a survival check was performed at 1 year. Results: We enrolled 1001 patients (82.0 years, 62.5% female, 63.7% New York Heart Association functional class III/IV at baseline) from 27 clinical sites in 8 countries across Europe and one site in Australia. Implantation of a single valve was successful in 97.5% of subjects. Valve hemodynamics at 30 days were substantially improved relative to baseline, with large aortic valve areas and low mean gradients across all implanted valve sizes (aortic valve areas were 1.7 ± 0.4, 1.7 ± 0.5, 1.8 ± 0.5, and 2.0 ± 0.5 cm2, and mean gradients were 7.0 ± 2.7, 7.5 ± 4.7, 7.3 ± 3.3, and 6.4 ± 3.3 mmHg for 23, 25, 27, and 29 mm valve sizes, respectively). Across all implanted valve sizes, most patients (77.1%) had no patient-prosthesis mismatch. Death from any cause within 1 year occurred in 13.7% of the patients in the first-generation DS group as compared with 11.0% in the second-generation DS group (p = 0.2). Conclusions: The Portico valve demonstrated excellent hemodynamic performance across all valve sizes in a large cohort of subjects implanted in experienced TAVI centers. One-year survival rates were favorable when using both the first-generation and second-generation (FlexNav) DSs in this high-risk cohort. ClinicalTrials.gov Identifier: NCT03752866.

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together.

We completely describe the structure of locally (soluble-by-finite) groups in which all abelian subgroups are locally cyclic‎. ‎Moreover‎, ‎we prove that Engel groups with the above property are locally nilpotent‎.

Abstract Soil movements produced around deep excavations are one of the main issues to be addressed during design and construction of underground structures in urban environment. Several methods to predict ground movements are currently available. Semi-empirical methods correlate displacements and simple geometrical features of the excavation; these methods predict separately transversal and longitudinal settlement troughs or at least provide a conservative envelope of them and they are mainly based on empirical data of excavations in clay. Numerical methods based on the solutions of FEM or DFM models usually provide prediction of the green field subsidence. In this paper existing 2D semi-empirical methods are first shortly reviewed. Some of these methods are then modified and combined into a new 3D analytical description of the subsidence trough around a deep excavation. The proposed two variable subsidence function depends on several parameters: four independent parameters defining the overall shape and the maximum settlement acting as a scale parameter. Settlement fields reproduced by a 3D FEM nonlinear parametric study of deep excavations inspired by real case studies are thus presented and discussed. The newly proposed 3D analytical description is applied to fit the FEM results and some fundamental relationships among geometrical features of the excavation pit and the 3D shape function parameters are identified. These relationships are validated via the application to three case studies of deep excavations in sand where the subsidence was controlled by the deformation of the retaining structures finding a satisfactory and encouraging agreement.

Prenatal alcohol exposure is responsible for increasing chronic disease risk in later life, including obesity and metabolic syndrome. Alcohol drinking may compromise endogenous antioxidant capacity, causing an increase in free radicals and reactive oxygen species in the newborn. Excessive reactive oxygen species could attack the cellular proteins, lipids, and nucleic acids, leading to cellular dysfunction. Moreover, oxidative stress could play a crucial role in the altered synthesis and release of neurotrophins and progressive mitochondrial modifications with uncontrolled apoptosis. This narrative review aims to underline the important role of alcohol abuse in oxidative stress events and consequent metabolic and neurocognitive impairments in children exposed to alcohol during gestational life.

Abstract Background Percutaneous left atrial appendage occlusion (LAAO) represents an alternative stroke prevention method in patients with atrial fibrillation and an increased bleeding risk, chronic kidney disease or contraindications to oral anticoagulants. Aim of our study was to evaluate the feasibility and safety of percutaneous LAAO in high-risk, frail patients having undergone transcatheter aortic valve implantation (TAVI). Methods Thirty-one patients having undergone TAVI and scheduled for LAAO were prospectively included in our study. Results Implantation was successful in 29 of 31 cases (93.5%).There were no patients that developed a major acute cardiovascular event, stroke, or device dislocation/embolization. There was a single case of major bleeding (3.2%) and 3 cases of acute kidney injury (9.7%). At 3 months, no patients experienced a stroke, one patient had a device-related thrombus (3.4%), one patient showed a significant peri-device leak, and one patient had a persistent iatrogenic atrial septal defect. Conclusions Our study shows that percutaneous LAAO may represent a feasible alternative strategy for stroke prevention, that can be safely performed in high-risk, multimorbid patients with high bleeding risk or contraindications to oral anticoagulation.

Background:. Hemorrhoidal artery ligation (HAL) may reduce postoperative pain and complications and shorten patients’ recovery when compared to standard hemorrhoidectomy. It is unclear if the Doppler guide (DG) is useful in reducing recurrence risk. Objective:. To compare two groups of patients (treated with DG-HAL or HAL) in terms of recurrence risk and patients’ satisfaction grade. Methods:. Between January 1, 2014 and January 31, 2021, 122 patients affected by grade II-III hemorrhoidal prolapse underwent DG-HAL or HAL at Chivasso Hospital, Italy. Mucopexy was routinely performed. After discharge, patients were subjected to 1-week, 1-, 3-, 6-, and 12-month clinical assessment. Thereafter, they were interviewed by telephone annually. Results:. Seventy-six (62.3%) DG-HAL and 46 (37.7%) HAL procedures were performed. Median surgical time was 30 (15–45) minutes for DG-HAL versus 25 (15–40) minutes for HAL (P = 0.005). No intraoperative complications occurred. Postoperative bleeding needing surgery occurred in 2 (1.6%) patients in the DG-HAL group. During a median follow-up of 46 months (6–86), we registered 18 (23.7%) recurrences in the DG-HAL group and 13 (28.3%) in the HAL one (P = 0.574). No cases of incontinence or anal stenosis occurred. No significant difference was observed between the two groups in terms of patients’ satisfaction. At multivariate analysis, age ≥ 65 years resulted a protective factor for recurrence (odds ratio 0.31; 95% confidence interval 0.09–0.98; P = 0.047). Conclusions:. In our study, the use of DG did not reduce recurrence risk. Operative time was significantly increased in the DG-HAL group.

The synergistic combination of Nafion and sulfonated graphene oxide (GOsulf) in nanocomposite membranes emerged as a promising strategy for advancing proton exchange membrane fuel cell (PEMFC) technology. In the pursuit of elucidating the effect of GOsulf introduction on transport properties and electrochemical performance of Nafion, this work provides a systematic study combining swelling tests, water release tests, 1H NMR characterization, and Electrochemical Impedance Spectroscopy (EIS) investigation. The incorporation of organomodified GO nanolayers alters the distribution of water molecules within the hydrophilic domains of Nafion and produces a considerable increase in the “bound-water” fraction. This increases its water retention capability while ensuring very high diffusivity even under high temperatures, i.e., 1.5 × 10−5 cm2 s−1 at 130 °C. These peculiar features enable Naf-GOsulf to successfully operate under a dehydrating environment, yielding a proton conductivity of 44.9 mS cm−1 at 30% RH.

A large scale approach for multifunctional smart display systems in traditional textiles has yet to be demonstrated. Here, authors present a foldable, rollable 46-inch smart textile lighting/display system for smart homes and internet of things applications via the systematic design and integration of versatile fibre devices into textile form factors.

Abstract Feasibility and efficacy of complex percutaneous coronary intervention (PCI) in the elderly, a more frail population due to more comorbidities is incompletely understood. We therefore set out to compare success and complication rate of PCI for chronic total occlusion (CTO) in octogenarians, in comparison to non-octogenarians. Data from 267 patients (58 patients over 80 years of age and 209 under 80 years of age) who had undergone CTO PCI were analyzed. To compare the results we calculated the propensity score and used inverse probability of treatment weighting. We evaluated demographic, clinical, angiographic, and periprocedural information. The median age of the total collective was 68 (31–90) years (octogenarian collective 82 (80–90) years vs non-octogenarians 65 (31–79) years). We observed a high success rate in both collectives (82.8% vs 90.4%, p = 0.10) and no difference in periprocedural complications or complications in the follow-up period. In our collective restenosis rate at follow-up was comparable to the propensity sore weighted population (11.3% vs 16.3%, p = 0.9). Our results show that CTO PCI in older patients is safe and feasible with comparable in-hospital and follow-up complication rates compared to a younger patient population.

Abstract A successful strategy for improving the safety issues of new‐generation lithium‐ion batteries is to replace liquid electrolytes with solid or quasi‐solid membranes, a procedure that ensures adequate ionic conductions and are mechanical strengths.

Surgical aortic valve replacement (SAVR) in kidney transplant recipients (KTR) is associated with high morbidity and mortality, and an increased risk of postoperative graft failure potentially leading to graft loss. Transcatheter aortic valve implantation (TAVI) emerged as an alternative in high-risk patients. However, data on TAVI in kidney transplant recipients are limited. We performed a retrospective analysis of 40 KTR in which aortic valve replacement was performed at our center between 2005 and 2015. The outcomes and follow-up of TAVI (n=20; 2010-2015) and SAVR (n=20; 2005-2015) were analyzed with respect to patient and graft survival. Baseline characteristics in both groups were comparable. Hospital stay after TAVI was significantly shorter compared to SAVR (19 [11.5-21.75] days vs. 33 [21-62] days, p=0.001). Acute graft failure occurred more frequently after SAVR (45% vs. 89.5%; p=0.006). Thirty-day mortality was 10% in both groups. However, in-hospital mortality reached 25% in the SAVR group (TAVI 10%), indicating a more complicated course after surgery. Moreover, during a median follow-up time of 1928 days in TAVI patients and 2717 days in patients after SAVR, graft loss occurred only in the surgically treated group (n=7). While one-year survival after TAVR was 90% compared to 69% after SAVR, long-term follow-up showed comparable results (at 5 years: TAVI 58% vs. 52% SAVR; log-rank-test: p=0.86). In KTR, TAVI can be performed with good mid- to long-term results. Compared to SAVR, renal outcomes seem to be improved after TAVI, suggesting better graft survival.

Among the newest antiepileptic drugs, brivaracetam (BRV), previously known as “ucb34714”, is one of the most interesting molecules available, increasingly getting the attention of researchers. The clinical efficacy of BRV as adjunctive therapy has been extensively assessed in six randomized, controlled, phase III trials, the results of which demonstrated BRV efficacy in reducing seizures at the dosage of 20–200 mg/day. However, to date, only few data on the pediatric population are available. Here we briefly report the data available on BRV and its usage in the pediatric population suffering from epilepsy to highlight the potential benefits of this drug in this population.

Bisphenol A (BPA), an endocrine-disrupting compound with estrogenic behavior, is of great concern within the scientific community due to its high production levels and increasing concentration in various surface aquifers. While several materials exhibit excellent capacity for the photocatalytic degradation of BPA, their powdered nature and poor chemical stability render them unsuitable for practical application in large-scale water decontamination. In this study, a new class of nanocomposite membranes based on sulfonated polyethersulfone (sPES) and multiwalled carbon nanotubes decorated with TiO2 nanoparticles (MWCNTs-TiO2) were investigated as efficient and scalable photocatalysts for the photodegradation of BPA in aqueous solutions. The MWCNTs-TiO2 hybrid material was prepared through a facile and inexpensive hydrothermal method and extensively characterized by XRD, Raman, FTIR, BET, and TGA. Meanwhile, nanocomposite membranes at different filler loadings were prepared by a simple casting procedure. Swelling tests and PFG NMR analyses provided insights into the impact of filler introduction on membrane hydrophilicity and water molecular dynamics, whereas the effectiveness of the various photocatalysts in BPA removal was monitored using HPLC. Among the different MWCNTs-TiO2 content nanocomposites, the one at 10 wt% loading (sP-MT10) showed the best photoactivity. Under UV irradiation at 254 nm and 365 nm for 240 min, photocatalytic oxidation of 5 mg/L bisphenol A by sP-MT10 resulted in 91% and 82% degradation, respectively. Both the effect of BPA concentration and the membrane regenerability were evaluated, revealing that the sP-MT10 maintained its maximum BPA removal capability over more than 10 cycles. Our findings indicate that sP-MT nanocomposite membranes are versatile, scalable, efficient, and highly reusable photocatalysts for the degradation of BPA, as well as potentially for other endocrine disruptors.

Nazareno Carullo,1 Maria Teresa Zicarelli,1 Alessandro Casarella,2 Ramona Nicotera,1 Alberto Castagna,2 Alessandra Urso,1 Pierangela Presta,1 Michele Andreucci,1 Emilio Russo,2 Davide Bolignano,1 Giuseppe Coppolino1 1Renal Unit, Department of Health Sciences, “Magna Graecia” University, Catanzaro, Italy; 2Department of Health Sciences, “Magna Graecia” University, Catanzaro, ItalyCorrespondence: Giuseppe CoppolinoRenal Unit, Department of Health Sciences, “Magna Graecia” University, Viale Europa - Germaneto, Catanzaro, 88100, ItalyTel +39 09613697170Email gcoppolino@unicz.itAbstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent single-gene disorder leading to renal failure. Current therapies are aimed to treat renal and extrarenal complications of ADPKD, but improved knowledge of the pathophysiological mechanisms leading to the generation and growth of cysts has permitted the identification of new drug candidates for clinical trials. Among these, in this review, we will examine above all the role of metformin, hypothesized to be able to activate the AMP-activated protein kinase (AMPK) pathway and potentially modulate some mechanisms implicated in the onset and the growth of the cysts.Keywords: cystogenesis, renal cells, metformin, chronic renal disease, renal tubule

Abstract Background the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy. Methods the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations. Results the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies. Conclusions adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety.