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Background: Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro. Despite this evidence, a definitive causal link between CNF1 and CRC was missing. Here we investigated whether CNF1 plays an active role in CRC onset by analyzing pro-carcinogenic key effects specifically induced by the toxin in vitro and in vivo., Methods: Viability assays, confocal microscopy of γH2AX and 53BP1 molecules and cytogenetic analysis were carried out to assess CNF1-induced genotoxicity on non-neoplastic intestinal epithelial cells. Caco-2 monolayers and 3D Caco-2 spheroids were used to evaluate permeability alterations specifically induced by CNF1, either in the presence or in the absence of inflammation. In vivo, an inflammatory bowel disease (IBD) model was exploited to evaluate the carcinogenic potential of CNF1. Immunohistochemistry and immunofluorescence stainings of formalin-fixed paraffin-embedded (FFPE) colon tissue were carried out as well as fecal microbiota composition analysis by 16 S rRNA gene sequencing., Results: CNF1 induces the release of reactive oxidizing species and chromosomal instability in non-neoplastic intestinal epithelial cells. In addition, CNF1 modifies intestinal permeability by directly altering tight junctions' distribution in 2D Caco-2 monolayers, and by hindering the differentiation of 3D Caco-2 spheroids with an irregular arrangement of these junctions. In vivo, repeated intrarectal administration of CNF1 induces the formation of dysplastic aberrant crypt foci (ACF), and produces the formation of colorectal adenomas in an IBD model. These effects are accompanied by the increased neutrophilic infiltration in colonic tissue, by a mixed pro-inflammatory and anti-inflammatory cytokine milieu, and by the pro-tumoral modulation of the fecal microbiota., Conclusions: Taken together, our results support the hypothesis that the CNF1 toxin from E. coli plays an active role in colorectal carcinogenesis. Altogether, these findings not only add new knowledge to the contribution of bacterial toxins to CRC, but also pave the way to the implementation of current screening programs and preventive strategies., Competing Interests: Declarations. Ethics approval: This study was carried out according to the European Guidelines for the Care and the Use for Laboratory Animals (authorization n° 787/21-PR). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Deep pressure therapy (DPT) is widely used to reduce anxiety in children with autism spectrum disorder (ASD), but evidence of its efficacy is limited., Objective: This study aims to design a usable, nonstigmatizing compressive armchair that can be easily controlled, electronically, by the user., Methods: A user-centered approach was used to assess the usability of the device. Testing was carried out in a day hospital for children with ASD in France, with a convenience sample of children with severe forms of ASD and intellectual deficiency (N=39). The Witteman design guideline was used. The System Usability Scale and time of use were reported., Results: The final product is a compressive armchair designed to be user centered, with 4 different cells that can be inflated to induce tailored pressure on the body. The pressure level is recorded electronically. Usability was between good and excellent. The device was used by 39 children, once or twice weekly, over a period of 31 months. Each session lasted between 3 and 20 minutes. The armchair takes up less space than a hug machine. Performing sessions with the chair is feasible., Conclusions: First clinical impressions show a decrease in anxiety, improved emotional regulation, and improved attention. DPT is widely used in occupational therapy and frequently requested by parents, but efficacy studies are too scarce to make evidence-based recommendations for its use. The results presented here support further controlled efficacy studies of DPT in the treatment of anxiety in children with ASD., (©Thomas Gargot, Amandine Vachaud, Clémence Gilard, Alexia Audrain, Marie Gomot, Marco Guidotti, Frédéric Briend, Joëlle Malvy, Frédérique Bonnet Brilhault. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 05.11.2024.)

A synthetic saponite clay containing structural Nb(V) metal centres (NbSAP) was investigated in the abatement of paraoxon-ethyl, an anti-cholinergic organophosphorus pesticide, under mild conditions (neutral pH, room temperature and ambient pressure) in heterogenous phase, without additional basic additives. The material was selected according to its high surface acidity and ease of preparation through a one-step hydrothermal synthesis. The presence of Nb(V) ions played a crucial role in efficiently catalysing the degradation of aggressive chemical substrates. A niobium(V) oxide with very low surface acidity was also tested as a reference material. The study employed a multi-technique approach to monitor the pesticide degradation pathway and by-products formed during abatement experiments in polar non-protic and aqueous solvents. Notably, in water, the concentration of paraoxon-ethyl significantly decreased by 82 % within the first hour of contact with the clay. Additionally, NbSAP demonstrated a good performance after three repeated catalytic cycles and subsequent reactivation., Competing Interests: 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., (© 2024 The Authors.)

Background: The olive fruit fly (OFF), Bactrocera oleae (Rossi), is the main insect pest of olive trees worldwide. Legislation limits to the use of some synthetic larvicidal insecticides is leading to the development of new control options for preventive control of adult flies. In the present study, the biological activity of four short-chain aliphatic aldehydes, namely hexanal, (E)-2-hexenal, heptanal and (E)-2-heptenal, previously reported as repellents to the OFF adults was investigated., Results: Electroantennography (EAG) recordings showed that antennae of OFF males and females are able to perceive the test compounds in a wide range of doses. In field trapping experiments, reservoir-type polypropylene (PP) membrane dispensers loaded with individual compounds did not elicit a significant attraction of OFF males and females. On the contrary, a significant reduction of male catches was noticed when sex pheromone dispensers and PP membrane dispensers, loaded with one of the test compounds, were applied on the same white sticky traps ≈20 cm apart. Likewise, male and female catches in yellow sticky traps baited with ammonium carbonate (AC) dispensers as food attractant were significantly reduced by the presence of PP membrane dispensers of individual aliphatic aldehydes on the same traps. In small plots control trials, solid formulations of the four aldehydes into a bentonite clay support induced a significant reduction of the OFF active infestation mainly when C 6 and C 7 aldehyde-activated bentonites were used., Conclusion: Short-chain aliphatic aldehydes showed inhibitory effects on sex pheromone and food attractant-mediated attraction of OFF. Results of field trials suggest potential of short-chain aliphatic aldehydes to develop new semiochemical-based OFF control options. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objectives: Among the complications of parotid surgery, facial palsy is frequent and burdened by high functional and social impact for the patient. There are few data on the efficacy of facial neuromuscular retraining (FNR) in patients with facial palsy after parotid surgery, and no data exist on its impact in timing and extent of recovery., Material and Methods: A retrospective study was conducted on patients undergoing FN sparing parotid surgery and suffering from postoperative facial palsy. Among 400 patients undergoing surgery between July 2016 and May 2023, those with the preservation of the FN and onset of facial palsy were selected. Nerve function was evaluated during 2 years follow up using the House-Brackman (H&Bs) and Sunnybrook scales (SBs)., Results: A total of 46 patients undergoing partial or total parotidectomy were included. At discharge 18 patients (39,1%) had IV to VI grade paralysis according to the H&Bs and the mean SBs value was 54. At 2 and 6 months after surgery, the average value of Sunnybrook increased to 76.5 and 95.4 respectively. After 12 months no patients with IV to VI grade paralysis were represent in our cohort. Two years after surgery, only five patients (10.9%) had persistent grade II paralysis according to HBs., Conclusions: Our study supports the efficacy of FNR in the rehabilitation of facial paralysis after nerve-sparing parotidectomy. The greater functional improvement is achieved within the first 6 months of rehabilitation. A significant improvement is detected still after 18 months, supporting the importance of long rehabilitation for patients without complete recovery after the first year., (© 2024. The Author(s).)

Objectives: The aim of this study is to compare voice outcomes in open partial horizontal laryngectomy vs. total laryngectomy (TL) with voice prosthesis., Methods: In this retrospective monocentric study patients undergoing OPHL or TL with voice prosthesis were enrolled during the usual oncological follow-up consultations at the Otolaryngology and Audiology Unit of a University Hospital in the period between July 2022 and June 2023. Acoustic analysis (F0, HNR, NHR), maximum phonation time, I-SECEL and INFV0 scale were used to assess voice outcome., Results: Forty-three patients were enrolled. Voices of patients undergoing LT were better in quality of voice (V0) at INFV0 scale. The scores in I-SECEL and acoustic analysis were comparable., Conclusions: Voice quality could be slight better in patients undergoing TL with voice prosthesis than those undergoing OPHL., (© 2024. The Author(s).)

A set of organic/inorganic layered materials was obtained by functionalizing a montmorillonite-containing bentonite natural clay with linear aliphatic C 6 or C 7 aldehydes through a cost-effective and technologically simple incipient-wetness deposition method. The solids were investigated by means of a multi-technique approach (X-ray powder diffraction, XRPD, scanning electron microscopy, SEM, Fourier-transform infrared spectroscopy, FT-IR, thermogravimetric analysis, TGA, elemental analysis and solid-state nuclear magnetic resonance, ssNMR) to clarify the nature of the deposited organic species and the mode of interaction between the aldehyde and the clay. Since both natural clays and short-chain linear aldehydes find application as alternative strategies in the control of the olive fruit fly, Bactrocera oleae , the hybrid layered materials were tested under real-life conditions and their insect-inhibiting capability was evaluated in open-field trials on olive tree orchards in Tuscany, Central Italy. Specific tests were conducted to evaluate the resistance of the solids to weathering and their capability to provide a constant and long-lasting release of the bioactive ingredient. Aldehyde-containing bentonite clays have shown promising performance in controlling B. oleae infestation (with up to 86-95% reduction of affected olive fruits) in open-field trials across two years in two locations with different pedological and meteo-climatic characteristics.

Purpose: A variety of lesions could arise from the GG area, or extend into this region from adjacent sites. The management of perigeniculate lesions includes observation, surgery, and radiation, according to the nature, the size of the lesion, and the accompanying symptoms. Preliminary experiences on the exclusive transcanal endoscopic approach to the GG area have shown safety and feasibility avoiding of any postauricular incision, or brain manipulation. The experience from two referral centers on patients treated for a GG lesion with a totally endoscopic approach is herein reported., Methods: Data about patients who underwent exclusive endoscopic approach to the GG area at the Otolaryngology Departments of the University Hospitals of Modena and Bologna between May 2017 and February 2022 were retrospectively collected., Results: The total number of patients included in our study was 11. 10 patients (91%) had progressive unilateral facial paralysis and 1 patient (11%) presented with chronic otorrhea. The mean largest diameter of the treated lesions was of 8 mm. The resection was extended to the fundus of the IAC in 2 patients (expanded approach). The remaining 9 patients (82%) underwent partial ossicular replacement prosthesis (PORP). No major complications occurred. Facial nerve outcomes were good in all patients and the mean ABG worsened from 12 dB pre-operatively to 22 dB post-operatively., Conclusions: The exclusively endoscopic approach to GG lesions represents a viable alternative to traditional microscopic approaches and may be included in the armamentarium of ear surgeons., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Somatosensory evoked potential (SEP) studies typically characterize short-latency components following median nerve stimulations of the wrist. However, these studies rarely considered 1 ) skin type (glabrous/hairy) at the stimulation site, 2 ) nerve being stimulated, and 3 ) middle-latency (>30 ms) components. Our aim was to investigate middle-latency SEPs following simple mechanical stimulation of two skin types innervated by two different nerves. Eighteen adults received 400 mechanical stimulations over four territories of the right hand (two nerves: radial/median; two skin types: hairy/glabrous skin) while their EEG was recorded. Four middle-latency components were identified: P50, N80, N130, and P200. As expected, significantly shorter latencies and larger amplitudes were found over the contralateral hemisphere for all components. A skin type effect was found for the N80; glabrous skin stimulations induced larger amplitude than hairy skin stimulations. Regarding nerve effects, median stimulations induced larger P50 and N80. Latency of the N80 was longer after median nerve stimulation compared with radial nerve stimulation. This study showed that skin type and stimulated nerve influence middle-latency SEPs, highlighting the importance of considering these parameters in future studies. These modulations could reflect differences in cutaneous receptors and somatotopy. Middle-latency SEPs can be used to evaluate the different steps of tactile information cortical processing. Modulation of SEP components before 100 ms possibly reflects somatotopy and differential processing in primary somatosensory cortex. NEW & NOTEWORTHY The current paper highlights the influences of stimulated skin type (glabrous/hairy) and nerve (median/radial) on cortical somatosensory evoked potentials. Mechanical stimulations were applied over four territories of the right hand in 18 adults. Four middle-latency components were identified: P50, N80, N130, and P200. A larger N80 was found after glabrous skin stimulations than after hairy skin ones, regardless of the nerve being stimulated. P50 and N80 were larger after median than radial nerve stimulations.

Horizontal gene transfer (HGT) in food matrices has been investigated under conditions that favor gene exchange. However, the major challenge lies in determining the specific conditions pertaining to the adapted microbial pairs associated with the food matrix. HGT is primarily responsible for enhancing the microbial repertoire for the evolution and spread of antimicrobial resistance and is a major target for controlling pathogens of public health concern in food ecosystems. In this study, we investigated Salmonella Heidelberg (SH) and Escherichia coli (EC) regarding gene exchange under conditions mimicking the industrial environment, with the coproducts whey (SL) and chicken juice (CJ). The S. Heidelberg strain was characterized by antibiotic susceptibility standards and PCR to detect the bla TEM gene. A concentration of 0.39 mg/mL was determined to evaluate the anti-conjugation activity of nanostructured lipid nanocarriers (NLCs) of essential oils to mitigate β-lactam resistance gene transfer. The results showed that the addition of these coproducts promoted an increase of more than 3.5 (whey) and 2.5 (chicken juice) orders of magnitude in the conjugation process ( p < 0.01), and NLCs of sage essential oil significantly reduced the conjugation frequency (CF) by 74.90, 90.6, and 124.4 times when compared to the transfers in the absence of coproducts and the presence of SL and CJ, respectively. For NLCs from olibanum essential oil, the decrease was 4.46-fold for conjugations without inhibitors and 3.12- and 11.3-fold in the presence of SL and CJ. NLCs associated with sage and olibanum essential oils effectively control the transfer of antibiotic resistance genes and are a promising alternative for use at industrial levels.

Varicocele treatment in infertility still remains controversial. It is clear, in fact, that in many patients, varicocele has no impact on fertility. Recent scientific evidence demonstrated that varicocele treatment is beneficial in improving semen parameters and pregnancy rate when an appropriate selection of patients is made. The purpose of treating varicocele in adults is mainly to improve current fertility status. On the other hand, the goal of treatment in adolescents is to prevent testicular injury and maintain testicular function for future fertility. Hence, the key to the success of varicocele treatment seems to be a correct indication. The aim of this study is to review and summarize current evidence in managing varicocele treatment focusing on the controversies regarding surgical indications in adolescent and adult patients, and in other specific situations such as azoospermia, bilateral or subclinical varicocele, and prior to ART.

This work describes the preparation, characterization and antimicrobial activity of four palladium(II) complexes, namely, [Pd(meg)(1,10-phen)] 1 , [Pd(meg)(PPh 3 ) 2 ] 2, [Pd(og)(1,10-phen)] 3 and [Pd(og)(PPh 3 ) 2 ] 4 , where meg = methyl gallate, og = octyl gallate, 1,10-phen = 1,10-phenanthroline and PPh 3 = triphenylphosphine. As to the chemical structures, spectral and physicochemical studies of 1 - 4 indicated that methyl or octyl gallate coordinates a palladium(II) ion through two oxygen atoms upon deprotonation. A chelating bidentate phenanthroline or two triphenylphosphine molecules complete the coordination sphere of palladium(II) ion, depending on the complex. The metal complexes were tested against the Mycobacterium tuberculosis H37Rv strain and 2 exhibited high activity (MIC = 3.28 μg/mL). As to the tests with Campylobacter jejuni , complex 1 showed a significant effect in reducing bacterial population (greater than 7 log CFU) in planktonic forms, as well as in the biomass intensity (IBF: 0.87) when compared to peracetic acid (IBF: 1.11) at a concentration of 400 μg/mL. The effect provided by these complexes has specificity according to the target microorganism and represent a promising alternative for the control of microorganisms of public health importance.

The bacterial product CNF1, through its action on the Rho GTPases, is emerging as a modulator of crucial signalling pathways involved in selected neurological diseases characterized by mitochondrial dysfunctions. Mitochondrial impairment has been hypothesized to have a key role in paramount mechanisms underlying Rett syndrome (RTT), a severe neurologic rare disorder. CNF1 has been already reported to have beneficial effects in mouse models of RTT. Using human RTT fibroblasts from four patients carrying different mutations, as a reliable disease-in-a-dish model, we explored the cellular and molecular mechanisms, which can underlie the CNF1-induced amelioration of RTT deficits. We found that CNF1 treatment modulates the Rho GTPases activity of RTT fibroblasts and induces a considerable re-organization of the actin cytoskeleton, mainly in stress fibres. Mitochondria of RTT fibroblasts show a hyperfused morphology and CNF1 decreases the mitochondrial mass leaving substantially unaltered the mitochondrial dynamic. From a functional perspective, CNF1 induces mitochondrial membrane potential depolarization and activation of AKT in RTT fibroblasts. Given that mitochondrial quality control is altered in RTT, our results are suggestive of a reactivation of the damaged mitochondria removal via mitophagy restoration. These effects can be at the basis of the beneficial effects of CNF1 in RTT., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Despite being considered fragile and fastidious, Campylobacter jejuni is the most prevalent cause of foodborne bacterial gastroenteritis, and chicken meat is considered the main vehicle of transmission to humans. This agent can survive adverse conditions in the form of biofilms, but extreme stress (nutritional, oxidative and thermal) promotes the acquisition of a state called viable but not culturable (VBNC). The emergence of this pathogen worldwide and the recent international requirements in its control instigated us to qualitatively and quantitatively estimate the time required for the acquisition of the VBNC form in 27 strains of C. jejuni , characterize morphological aspects, determine its adaptive and invasive potential and perform comparative metabolomic evaluation. Extreme stress promoted the complete acquisition of the VBNC form in a mean time of 26 days. Starting from an average initial count of 7.8 log CFU/mL, the first four days determined the greatest average reduction of the culturable form of 3.2 log CFU/mL. The scanning and transmission image analyses showed a transition from the typical viable form (VT) to the VBNC form, with initial acquisition of the straight rod shape, followed by loss of the flagella and subdivision into two to 11 imperfect cocci arranged in a chain and rich in cellular content, until their individual release. RT-PCR identified the presence of ciaB and p19 transcripts in the 27 cultivable C. jejuni strains, a character maintained in the VBNC form only for p19 and in 59.3% (16/27) of the VBNC strains for the ciaB gene. The average inoculation of 1.8 log CFU/mL of C. jejuni VBNC into primary chicken embryo hepatocyte cells promoted the occurrence of apoptosis processes significantly after 24 hours of contact by one of the strains tested. In C. jejuni VBNC, we detected higher expression of metabolites linked to protective and adaptation mechanisms and of volatile organic precursor compounds indicative of metabolism interruption. The oscillations in the time of acquisition of the VBNC form together with the presence of transcripts for ciaB and p19 , the identification of cell lysis and metabolites that ensure the maintenance of the pathogen alert to the fact that C. jejuni VBNC remains virulent and adapted to stress, which makes evident the potential danger of this latent form, which is not detectable by official methodologies., Competing Interests: The 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 © 2023 Santos, Rossi, Braz, Fonseca, Guidotti–Takeuchi, Alves, Beletti, Almeida-Souza, Maia, Santos, de Souza and Melo.)

This study aimed at evaluating the autonomic response to pleasant affective touch in children with Autism Spectrum Disorders (ASD) and age-matched typically developing (TD) peers, thanks to multiple autonomic nervous system (ANS) parameters and by contrasting CT (C-tactile fibers) high- vs. low-density territory stimulations. We measured pupil diameter, skin conductance, and heart rate during gentle stroking of two skin territories (CT high- and low-density, respectively, forearm and palm of the hand) in thirty 6-12-year-old TD children and twenty ASD children. TD children showed an increase in pupil diameter and skin conductance associated with a heart rate deceleration in response to tactile stimulations at the two locations. Only the pupil was influenced by the stimulated location, with a later dilation peak following CT low-density territory stimulation. Globally, ASD children exhibited reduced autonomic responses, as well as different ANS baseline values compared to TD children. These atypical ANS responses to pleasant touch in ASD children were not specific to CT-fiber stimulation. Overall, these results point towards both basal autonomic dysregulation and lower tactile autonomic evoked responses in ASD, possibly reflecting lower arousal and related to social disengagement.

This Review provides a summary of the use and the role of coordination complexes as precursors for the generation of heterogeneous catalysts for oxidation reactions of interest for fine chemical synthesis. Specific attention is paid to the comprehension of phenomena explaining the formation of active sites in heterogeneous catalysts. Different families of coordination precursors are considered. For each example, a brief critical description of the synthesis, characterization, and catalytic performance is reported. Special attention is paid to the chemical environment of the first coordination sphere of the active metal centre. The catalysts obtained by heterogenization, grafting, or anchoring of homogeneous catalysts can therefore exhibit enhanced catalytic performance by merging advantages of both homogeneous and heterogeneous systems. The deposition of coordination complexes over a preformed support is indeed a conceptually versatile strategy to design novel catalysts with tuned and controlled properties., (© 2022 Wiley-VCH GmbH.)

Aim: This observational and repeated measures study assesses the impact of the first, most restrictive, COVID-19 lockdown in France on children with autism spectrum disorder (ASD) and their families., Method: During the first COVID-19 lockdown, families of ASD children enrolled in the day-care centre of the child and adolescent psychiatry department of the Tours University Hospital were contacted weekly. A total of 95 parents took part in this study between the 18th of March and the 8th of May 2020. Advice and personalized support materials were provided by professionals involved in children's care. Questions regarding clinical outcomes were addressed to parents, and their assessments were reported on a 5-point Likert scale. Two time points were considered: the first 3 weeks and the three last weeks of the lockdown period., Results: No difference was highlighted between clinical scores collected at the beginning and at the end of the lockdown. No effect of intellectual disability, accommodation type (house or apartment) or parental status was observed. The reasons for the relatively minor impact of the COVID-19 lockdown observed in this study are discussed., Conclusions: Individualized and regular support provided by caregivers, familiar with ASD children's clinical specificities, in the context of a trusted relationship with parents may have contributed to the stability of this population. This 'tailor-made' approach should be promoted, in order to help support families of ASD children in this challenging period., (© 2022 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Considering the suspected involvement of the autonomic nervous system (ANS) in several neurodevelopmental disorders, a description of its tonus in typical populations and of its maturation between childhood and adulthood is necessary. We aimed to arrive at a better understanding of the maturation of the sympathetic (SNS) and parasympathetic (PNS) tonus by comparing children and adults at rest, via recordings of multiple ANS indices. We recorded simultaneously pupil diameter, electrodermal activity (EDA) and cardiac activity (RR interval and HRV: heart rate variability) in 29 children (6-12 years old) and 30 adults (20-42 years old) during a 5-min rest period. Children exhibited lower RR intervals, higher LF peak frequencies, and lower LF/HF (low frequency/high frequency) ratios compared to adults. Children also produced more spontaneous EDA peaks, reflected in a larger EDA AUC (area under the curve), in comparison with adults. Finally, children displayed a larger median pupil diameter and a higher pupillary hippus frequency than adults. Our results converged towards higher SNS and PNS tones in children compared to adults. Childhood would thus be characterized by a high autonomic tone, possibly reflecting a physiological state compatible with developmental acquisitions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The use of essential oils (EO) loaded with nanoparticles is the most promising alternative to increase food quality and safety. Interesting works describe the antimicrobial properties of EO for pathogen control in natural and processed foods for human health and animal production, also contributing to sustainability. Their association with different nanosystems allows novel developments in the micronutrition, health promotion, and pathogen control fields, preventing the aggravation of bacterial microevolution and combating antibiotic resistance. Benefits to the environment are also provided, as they are biodegradable and biocompatible. However, such compounds have some physicochemical properties that prevent commercial use. This review focuses on recent developments in antimicrobial EO-based nanoparticles and their application in different food matrices.

Intermittent photic stimulation (IPS) is a useful technique in electroencephalography (EEG) to investigate the neurophysiological anomalies of brain activity. Although not an active task, IPS has also been explored in ASD; it is thought to capture local potential oscillators at specific frequencies and perhaps tap into rhythmic activity in a way that general resting-state recordings cannot. Previous studies suggest that individuals with ASD showed photic driving reactivity predominantly at lower frequencies of stimulation. In our study we used IPS to measure rhythmic oscillatory activity in a sample of 81 ASD children. We found a significant correlation linking ASD children with photic driving activation only at low frequencies (δθ band) and increased severity of "restricted behavior". This suggests that ASD children with higher severity of restricted behaviors could have a hypersynchronous θ power and an impaired resonance synchronization at middle-ranged frequencies (α). Furthermore, we found some evidence of hemispherical oscillatory asymmetry linked particularly to behavioral impairments. This result is in line with the EEG pattern model indicating a "U-shaped profile" of electrophysiological power alterations with excess power in low- and high-frequency bands and a reduction of power in the middle-ranged frequencies. IPS technique in electroencephalography is confirmed to reveal EEG biomarkers in autistic children, with a focus on spectral power, coherence, and hemisphere asymmetries.

Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed effective antimicrobial measures. The minimum inhibitory concentration was evaluated for seven antimicrobials, isolated and combined with the copper (II) complex [Cu(4-FH)(phen)(ClO 4 ) 2 ] (4-FH = 4-fluorophenoxyacetic acid hydrazide and phen = 1,10-phenanthroline), known as DRI-12, in planktonic and sessile ST. In parallel, 42 resistance genes were screened (PCR/microarray). All strains were multidrug resistant (MDR). Resistance to carbapenems and polymyxins (86 and 88%, respectively) have drawn attention to the emergence of the problem in Brazil, and resistance is observed also to CIP and CFT (42 and 67%, respectively), the drugs of choice in treatment. Resistance to beta-lactams was associated with the genes bla TEM / bla CTX-M in 39% of the strains. Lower concentrations of DRI-12 (62.7 mg/L, or 100 μM) controlled planktonic and sessile ST in relation to AMP/SUL/TET and AMP/SUL/TET/COL, respectively. The synergistic effect provided by DRI-12 was significant for COL/CFT and COL/AMP in planktonic and sessile ST, respectively, and represents promising alternatives for the control of MDR ST.

The removal of paramagnetic metal ions with different charges and ionic radii ( i.e. Gd 3+ , Cu 2+ , and Co 2+ ) from aqueous solutions was carried out by using a Na + -exchanged synthetic saponite clay. Saponite, composed of sub-micrometer particles and characterized by high cation-exchange capacity, was prepared through a classical low-cost hydrothermal approach. The metal ion uptake tests were performed in water at pH = 5.5 and 3.0, and the capture process was monitored in real time by 1 H-NMR relaxometry. The experimental data were confirmed by the conventional ICP-OES technique. Details of the uptake process kinetics were extrapolated from the NMR analyses as well. Saponite showed good sorption capacity for all selected metal ions. The regeneration of the solid sorbent after metal uptake was also analysed, obtaining encouraging results.

Objective: As the COVID-19 pandemic continues, the impact on neuropsychology trainees continues to evolve. This paper describes the results of a survey of neuropsychology trainee (graduate student through postdoctoral resident) perspectives on the COVID-19 pandemic and compares them to a previous survey conducted in Spring 2020., Method: The survey used several questions from the 2020 survey and added applicable new questions based on the results of the 2020 survey. The survey was distributed to listservs, training directors, and student organizations in neuropsychology with snowball sampling used., Results: Respondents were primarily female (82.4%) and white (63%). The majority of trainees (66%) reported loss of clinical hours. Interestingly, the average training time missed was approximately 3.36 weeks (SD = 9.27). Trainees continue to report that they have experienced increased anxiety, depression, and stress since the beginning of the pandemic; however, compared to a prior survey, rates of increased anxiety/stress remained stable, but more trainees reported increased depression. Approximately 31% of trainees reported that they were differentially impacted by the pandemic due to racial/ethnic background and female trainees were more likely to report increased personal stress, anxiety and depression than their male counterparts., Conclusions: Results suggest continued wide-reaching pandemic related impacts on neuropsychology trainees. For example, trainees continue to be concerned about the impact of lost clinical hours on their professional futures. The most notable of the personal impacts included increased rates of mental health concerns and differential impacts on trainees from ethnoracial minority communities. Recommendations are provided to assist trainees in coping with pandemic-related disruptions.

Early intervention programs positively affect key behaviors for children with autism spectrum disorder (ASD). However, most of these programs do not target children with severe autistic symptomatology associated with intellectual disability (ID). This study aimed to investigate the psychological and clinical outcomes of children with severe autism and ID enrolled in the Tailored and Inclusive Program for Autism-Tours (TIPA-T). The first step of the TIPA-T is the Exchange and Development Therapy (EDT): an individual neurofunctional intervention consisting of one-to-one exchanges between a child and a therapist taking place in a pared-down environment. It aims to rehabilitate psychophysiological abilities at the roots of social communication through structured sequences of "social play." Cognitive and socio-emotional skills and general development were evaluated with the Social Cognitive Evaluation Battery scale and the Brunet-Lézine Scale-Revised, respectively, before and after 9 months of intervention in 32 children with ASD and ID. Autistic symptomatology was evaluated with the Behavior Summarized Evaluation-Revised scale at five time-points in a subset of 14 children, both in individual and group settings. Statistically significant post-intervention improvements were found in cognitive and socio-emotional skills. All but one child showed improvements in at least one social domain, and 78% of children gained one level in at least four social domains. Twenty-nine children improved in cognitive domains, with 66% of children improving in at least three cognitive domains. Autistic symptomatology evaluated in one-to-one settings significantly decreased with therapy; this reduction was observed in more than 85% of children. In group settings, autistic symptomatology also decreased in more than 60% of children. Global developmental age significantly increased by 3.8 months. The TIPA-T, including EDT in particular, improves socio-emotional skills of most children with ASD and reduces autistic symptomatology, yet with heterogeneous outcomes profiles, in line with the strong heterogeneity of profiles observed in ASD. At the group level, this study highlights the benefits of the TIPA-T for children with severe autism and associated ID. Assessment of autistic core symptoms showed an improvement of social interaction, both in one-to-one and group evaluations, demonstrating the generalizability of the skills learned during the EDT., Competing Interests: J-LA is the author of the SCEB edited in the Pearson France-ECPA. 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 © 2021 Blanc, Latinus, Guidotti, Adrien, Roux, Dansart, Barthélémy, Rambault, Bonnet-Brilhault and Malvy.)

The aim of the study was to evaluate the genotypic and phenotypic characteristics of 20 strains of S. Heidelberg ( S H) isolated from broilers produced in southern Brazil. The similarity and presence of genetic determinants linked to virulence, antimicrobial resistance, biofilm formation, and in silico -predicted metabolic interactions revealed this serovar as a threat to public health. The presence of the ompC , invA , sodC , avrA , lpfA , and agfA genes was detected in 100% of the strains and the luxS gene in 70% of them. None of the strains carries the bla SHV , mcr-1, qnrA, qnrB , and qnrS genes. All strains showed a multidrug-resistant profile to at least three non-β-lactam drugs, which include colistin, sulfamethoxazole, and tetracycline. Resistance to penicillin, ceftriaxone (90%), meropenem (25%), and cefoxitin (25%) were associated with the presence of bla CTX-M and bla CMY-2 genes. Biofilm formation reached a mature stage at 25 and 37°C, especially with chicken juice (CJ) addition. The sodium hypochlorite 1% was the least efficient in controlling the sessile cells. Genomic analysis of two strains identified more than 100 virulence genes and the presence of resistance to 24 classes of antibiotics correlated to phenotypic tests. Protein-protein interaction (PPI) prediction shows two metabolic pathways correlation with biofilm formation. Virulence, resistance, and biofilm determinants must be constant monitoring in S H, due to the possibility of occurring infections extremely difficult to cure and due risk of the maintenance of the bacterium in production environments., Competing Interests: The 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 © 2021 Melo, Galvão, Guidotti-Takeuchi, Peres, Fonseca, Profeta, Azevedo, Monteiro, Brenig and Rossi.)

For the first time, the co-presence in the saponite structure of luminescent Eu III and catalytic Nb V metal sites was exploited for the simultaneous detection and catalytic abatement of sulfur-containing blister chemical warfare agents. Metal centers were introduced in structural positions of the saponite (in the interlayer space or inside the inorganic framework) following two different synthetic methodologies. The functionalized saponites were able to reveal the presence of a sulfur mustard simulant (2-chloroethyl)ethyl sulfide (CEES) after few seconds of contact time and more than 80 % of the substrate was catalytically decomposed after 24 h in the presence of aqueous hydrogen peroxide., (© 2020 Wiley-VCH GmbH.)

A diluted 3% w/w hydrogen peroxide solution acidified to pH 2.5 by adding citric acid inactivated SARS-CoV-2 virus by more than 4 orders of magnitude in 5 min. After a contact time of 15 min, no viral replication was detected. Aqueous solutions of sodium percarbonate inactivated coronavirus by >3 log 10 diminution in 15 min. Conversely, H 2 O 2 solutions with no additives displayed a scarce virucidal activity (1.1 log 10 diminution in 5 min), confirming that a pH-modifying ingredient is necessary to have a H 2 O 2 -based disinfectant active against the novel coronavirus., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

The ability of transplanted lichen Evernia (E.) prunastri (L.) to act as a high spatial biomonitoring tool for 14 polybrominated diphenyl ethers (PBDEs) was evaluated at 23 monitoring sites in a very polluted area in central Italy. The selected area is characterized by the presence of numerous emission sources, such as waste-to-energy plant, steel plant, vehicular traffic, and domestic heating. Transplanted E. prunastri proved to be a useful tool to biomonitor PBDEs, due to its ability to bioaccumulate individual congeners in varying concentrations in relation to the strength of the emission sources present over the territory. PBDEs levels widely ranged from 132 to 24,237 ng kg -1 dry weight, according to the sources of emission located around the monitoring sites. The highest concentrations were detected at the sites close to the municipal solid waste incinerator, steel plant, and high busy roads, confirming their important role as PBDEs emissions sources., 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 © 2020 Elsevier B.V. All rights reserved.)

Any release of radioactive cesium-137, due to unintentional accidents in nuclear plants, represents a dangerous threat for human health and the environment. Prussian blue has been widely studied and used as an antidote for humans exposed to acute internal contamination by Cs-137, due to its ability to act as a selective adsorption agent and to its negligible toxicity. In the present work, the synthesis protocol has been revisited avoiding the use of organic solvents to obtain Prussian blue nanoparticles with morphological and textural properties, which positively influence its Cs + binding capacity compared to a commercially available Prussian blue sample. The reduction of the particle size and the increase in the specific surface area and pore volume values compared to the commercial Prussian blue reference led to a more rapid uptake of caesium in simulated enteric fluid solution (+35% after 1 h of contact). Then, after 24 h of contact, both solids were able to remove >98% of the initial Cs + content. The Prussian blue nanoparticles showed a weak inhibition of the bacterial luminescence in the aqueous phase and no chronic detrimental toxic effects.

Several chronic neuroinflammatory diseases, including Parkinson's disease (PD), have the so-called 'redox imbalance' in common, a dynamic system modulated by various factors. Among them, alteration of the mitochondrial functionality can cause overproduction of reactive oxygen species (ROS) with the consequent induction of oxidative DNA damage and apoptosis. Considering the failure of clinical trials with drugs that eliminate ROS directly, research currently focuses on approaches that counteract redox imbalance, thus restoring normal physiology in a neuroinflammatory condition. Herein, we used SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA), a neurotoxin broadly employed to generate experimental models of PD. Cells were pre-treated with the Rho-modulating Escherichia coli cytotoxic necrotizing factor 1 (CNF1), before the addition of 6-OHDA. Then, cell viability, mitochondrial morphology and dynamics, redox profile as well as autophagic markers expression were assessed. We found that CNF1 preserves cell viability and counteracts oxidative stress induced by 6-OHDA. These effects are accompanied by modulation of the mitochondrial network and an increase in macroautophagic markers. Our results confirm the Rho GTPases as suitable pharmacological targets to counteract neuroinflammatory diseases and evidence the potentiality of CNF1, whose beneficial effects on pathological animal models have been already proven to act against oxidative stress through an autophagic strategy.

Some toxigenic bacteria produce protein toxins with carcinogenic signatures, which either directly damage DNA or stimulate signalling pathways related to cancer. So far, however, only a few of them have been proved to favour the induction or progression of cancer. In this work, we report that the Rho-activating Escherichia coli protein toxin, cytotoxic necrotising factor 1 (CNF1), induces epithelial to mesenchymal transition (EMT) in intestinal epithelial cells. EMT is a crucial step in malignant tumour conversion and invasiveness. In the case of CNF1, it occurs by up-regulation of the transcription factors ZEB1 and Snail1, delocalisation of E-cadherin and β-catenin, activation of the serine/threonine kinase mTOR, accelerated wound healing, and invasion. However, our results highlight that nontransformed epithelial cells entail the presence of inflammatory factors, in addition to CNF1, to acquire a mesenchymal-like behaviour. All this suggests that the surrounding microenvironment, as well as the cell type, dramatically influences the CNF1 ability to promote carcinogenic traits., (© 2019 John Wiley & Sons Ltd.)

Native and transplanted lichens were analyzed as bioaccumulators of airborne particulate matter (PM) in an eastern district of Rome, Italy, where frequent fraudulent fires are set to recover metals, mostly copper, from waste electrical and electronic equipment (WEEE). The presence of native lichens was scarce, due to the drought of spring-summer 2017, thus, sampling was extended to a neighboring area for toughening the dataset to a similar context. The magnetic analyses revealed intense properties connected to the anthropic complexity of the zone, where industrial, traffic and arson-related dusts are emitted and bio-accumulated. Magnetic and chemical analyses were compared, leading to significant linear correlations between the concentration dependent magnetic parameters (susceptibility, saturation magnetization and saturation remanence) and the concentration of heavy metals, among which copper, chrome, lead and zinc. Moreover, selected magnetic particles were chemically and morphologically characterized by Scanning Electron Microscope and Energy Dispersion System microanalyses. Magnetic particles resulted incorporated into the lichens' tissues and their composition, morphology and grain size strongly supported their anthropogenic, mostly combustion-related, origin. Even if, given the complexity of the area, it was not feasible to fully discriminate the multiple anthropogenic sources, magnetic biomonitoring of lichens, especially when combined with microtextural and compositional analyses, confirmed to be an excellent methodology for a rapid characterization of environmental pollution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The study was aimed to evaluate the ability of native lichen Xanthoria (X.) parietina to biomonitor and bioaccumulate some heavy metals (As, Cd, Co, Cr, Ni, Pb), PAHs, PCDDs, PCDFs, PCBs and PBDEs and to evaluate the use of the native X. parietina as a multi-tracer tool for scenarios characterized by different anthropogenic pressures. Samples of native X. parietina were collected in six different sites (two green, two residential and two industrial areas, respectively) and analyzed for the target compounds. The results show that X. parietina was a useful tool for the biomonitoring of air quality in the selected areas, and was able to bioaccumulate all the studied metals and POPs. In particular, the total concentrations dry weight (dw) ranged between 8.1 and 103.4 mg kg -1 for metals, from 113 × 10 3 to 183 × 10 3  ng kg -1 for PAHs, from 868 to 7685 ng kg -1 for PCBs, from 14.3 to 113.8 ng kg -1 for PCDDs/Fs (∑TEq = 0.9-7.1), and from 194 to 554 ng kg -1 for PBDEs. Besides, in general, the levels of analytes recovered in the different samples of lichen show an increasing trend from green to industrial sites, especially for PCBs (mean values equal to 1218, 4253 and 7192 ng kg -1 respectively for green, residential and industrial areas). The statistical approach, based on Pearson's correlation and principal component analysis tests, showed that one of the industrial sites was well-separated from the others, that resulted grouped due to some similarities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In hypertensive retinopathy, the retinal damage due to high blood pressure is accompanied by increased expression of Glial Fibrillary Acidic Protein (GFAP), which indicates a role of neuroinflammatory processes in such a retinopathy. Proteins belonging to the Rho GTPase family, particularly Rac1, are involved in the activation of Müller glia and in the progression of photoreceptor degeneration, and may thus represent a novel candidate for therapeutic intervention following central nervous system inflammation. In this paper, we have observed that topical administration as eye drops of Cytotoxic Necrotizing Factor 1 (CNF1), a Rho GTPase modulator, surprisingly improves electrophysiological and behavioral visual performances in aged spontaneously hypertensive rats. Furthermore, such functional improvement is accompanied by a reduction of Rac1 activity and retinal GFAP expression. Our results suggest that Rac1 inhibition through CNF1 topical administration may represent a new strategy to target retinal gliosis., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Telemedicine has changed over the last years, becoming an integrated service used in various clinical settings such as stroke units or radiological departments, but also as an important tool for home rehabilitation. Assessment of usefulness and efficiency of performing teleconsultations to manage stroke from acute care hospital to tertiary care rehabilitation hospital has not been referred by scientific literature., Aim: This article analyzes the process of discharging stroke patients from acute care to intensive rehabilitation, based on the comparison between conventional bedside patient evaluations and teleconsultation patient evaluations, to assess efficiency and efficacy of two different discharging workflows., Design: Retrospective study., Setting: Consultations were carried out between the Acute Care Stroke Unit and the Stroke Rehabilitation Unit of Valduce Hospital System., Population: The study included 257 stroke patients who underwent physiatric consultation during 2 years considered in this study and 101 patients were considered eligible for intensive rehabilitation treatment after a physiatric consultation., Methods: We compared the efficiency and efficacy of the dismission workflow of bedside medical consultation and teleconsultation over a 12 months period. We considered the following outcome measures: time elapsed between consultation and Rehabilitation Unit admission, number of re-admissions to acute care hospital, complications occurred during rehabilitation, length of stay in the rehabilitation hospital and clinical outcomes of rehabilitation process., Results: We observed a significant reduction in waiting time from the acute event to the admission in rehabilitation department, an improvement in efficiency of the admission process itself in the Rehabilitation Unit and a reduction of clinical complications occurred during rehabilitation period, without changes in rehabilitative outcomes., Conclusions: It has been highlighted that the use of telemedicine to perform medical consultation as a tool to evaluate patients eligible for tertiary care rehabilitation hospital admission from Stroke Care Unit is feasible and more efficient when compared with conventional bedside consultations., Clinical Rehabilitation Impact: This study reveals teleconsultations as a useful tool to improve efficiency of the stroke management workflow.

Plasmodium falciparum severe malaria causes more than 400,000 deaths every year. One feature of P. falciparum-parasitized erythrocytes (pRBC) leading to cerebral malaria (CM), the most dangerous form of severe malaria, is cytoadherence to endothelium and blockage of the brain microvasculature. Preventing ligand-receptor interactions involved in this process could inhibit pRBC sequestration and insurgence of severe disease whilst reversing existing cytoadherence could be a saving life adjunct therapy. Increasing evidence indicate the endothelial Rho signaling as a crucial player in malaria parasite cytoadherence. Therefore, we have used the cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli protein able to modulate the activity of Cdc42, Rac, and Rho, three subfamilies of the Rho GTPases family, to study interactions between infected erythrocytes and cerebral endothelium in co-culture models. The main results are that CNF1 not only prevents cytoadherence but, more importantly, induces the detachment of pRBCs from endothelia monolayers. We first observed that CNF1 does affect neither parasite growth, nor the morphology and concentration of knobs that characterize the parasitized erythrocyte surface, as viewed by scanning electron microscopy. On the other hand, flow cytometry experiments show that cytoadherence reversion induced by CNF1 occurs in parallel with a decreased ICAM-1 receptor expression on the cell surface, suggesting the involvement of a toxin-promoted endocytic activity in such a response. Furthermore, since the endothelial barrier functionality is compromised by P. falciparum, we conducted a permeability assay on endothelial cells, revealing the CNF1 capacity to restore the brain endothelial barrier integrity. Then, using pull-down assays and inhibitory studies, we demonstrated, for the first time, that CNF1 is able not only to prevent but also to cause the parasite detachment by simultaneously activating Rho, Rac and Cdc42 in endothelial cells. All in all our findings indicate that CNF1 may represent a potential novel therapeutic strategy for preventing neurological complications of CM., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) represents a challenge for the urologist, since the therapeutic efficacy does not always result in a satisfactory quality of life for the patients. Often the side effects of the medications used (antiinflammatories, antibiotics, alpha blockers) far outweighs the benefits gained with their admission. The choice of nutraceutical medications is preferred for their effectiveness, that has been accepted and proven by the scientific community, and for the low incidence of side effects. The objective of this study to compare the therapeutic efficacy of the flower pollen extracts (Deprox®) versus Bioflavonoids in terms of reduction of symptoms, and in the average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and to evaluate the quality of life improvement of the patients affected by CP/CPPS., Methods: Among the 68 patients presented with prostatic symptoms to the Hospital "Umberto I" in Rome, Italy between March 2016 and June 2016, 54 patients met the clinical diagnosis of CP/CPPS (class IIIa or IIIb according to the NIH classification). The patients were assigned to either treatment with Deprox® or quercetin based on a randomization scheme previously determined.The NIH- CPSI, IPSS, QoL questionnaires were administered. Every patient underwent bacterial cultures and trans-rectal ultrasound., Results: There was a statistically significant improvement of the NIH-CPSI score and QoL in the Deprox® group (p = < 0.0001 and p = 0.003 respectively). The average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was statistically significant (p = 0.0019). In the absence of efficacy of the "conventional" medications, which also carries significant side effects, the dietary supplements may represent a valid alternative., Conclusions: DEPROX® has demonstrated a significant improvement of the symptoms and quality of life of patients diagnosed with by CP/CPPS. Furthermore, there was a statistical difference in the average waiting time of the variation of the NIH-CPSI) score without side effects as compared to the bioflavonoids complex with quercetin.

The broad challenges of energy and environment have become a main focus of research efforts to develop more active and selective catalytic systems for key chemical transformations. Surface organometallic chemistry (SOMC) is an established concept, associated with specific tools, for the design, preparation and characterization of well-defined single-site catalysts. The objective is to enter a catalytic cycle through a presumed catalytic intermediate prepared from organometallic or coordination compounds to generate well defined surface organometallic fragments (SOMFs) or surface coordination fragments (SCFs). These notions are the basis of the "catalysis by design" strategy ("structure-activity" relationship) in which a better understanding of the mechanistic aspects of the catalytic process led to the improvement of catalyst performances. In this review the application of SOMC strategy for the design and preparation of catalysts for industrially relevant processes that are crucial to the energy and environment is discussed. In particular, the focus will be on the conversion of energy-related feedstocks, such as methane and higher alkanes that are primary products of the oil and gas industry, and of their product of combustion, CO2, whose efficient capture and conversion is currently indicated as a top priority for the environment. Among the main topics related to energy and environment, catalytic oxidation is also considered as a key subject of this review.

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1), which acts on the Rho GTPases that are key regulators of the actin cytoskeleton, is emerging as a potential therapeutic tool against certain neurological diseases characterized by cellular energy homeostasis impairment. In this brief communication, we show explorative results on the toxin’s effect on fibroblasts derived from a patient affected by myoclonic epilepsy with ragged-red fibers (MERRF) that carries a mutation in the m.8344A>G gene of mitochondrial DNA. We found that, in the patient’s cells, besides rescuing the wild-type-like mitochondrial morphology, CNF1 administration is able to trigger a significant increase in cellular content of ATP and of the mitochondrial outer membrane marker Tom20. These results were accompanied by a profound F-actin reorganization in MERRF fibroblasts, which is a typical CNF1-induced effect on cell cytoskeleton. These results point at a possible role of the actin organization in preventing or limiting the cell damage due to mitochondrial impairment and at CNF1 treatment as a possible novel strategy against mitochondrial diseases still without cure.

A class of heterogeneous catalysts based on commercial bentonite from natural origin, containing at least 80 wt% of montmorillonite clay, was designed to transform selectively and under mild conditions toxic organosulfur and organophosphorus chemical warfare agents into non-noxious products with a reduced impact on health and environment. The bentonite from the natural origin was modified by introducing iron species and acid sites in the interlayer space, aiming to obtain a sorbent with strong catalytic oxidising and hydrolytic properties. The catalytic performance of these materials was evaluated in the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, in the presence of aqueous hydrogen peroxide as an oxidant. A new decontamination formulation was, moreover, proposed and obtained by mixing sodium perborate, as a solid oxidant, to iron-bentonite catalysts. Solid-phase decontamination tests, performed on a cotton textile support contaminated with organosulfide and organophosphonate simulant agents revealed the good activity of the solid formulation, especially in the in situ detoxification of blistering agents. Tests carried out on the real blistering warfare agent, sulfur mustard (HD agent), showed that, thanks to the co-presence of the iron-based clay together with the solid oxidant component, a good decontamination of the test surface from the real warfare agent could be achieved (80% contaminant degradation, under ambient conditions, in 24 h).

Background: In the last years several studies have investigated the effects of some air pollutants on cardiovascular diseases (CVD), but the results are not conclusive. Aim of this study was to investigate the association between short-term exposure to ambient air pollution and CVD events in a long-term observational period., Methods: All CVD events (myocardial infarction - MI and ischemic stroke - IS) which occurred in residents of Como between January 2005 and December 2014 were included. Demographics and main vascular risk factors were registered for each patient. Principal meteorological variables and four ambient particles (O 3 , SO 2 , NO 2 , PM 10 ) were recorded. Statistical analysis was performed using linear regression (GLM) and a generalized additive model (GAM) estimating Poisson distribution and adjusted for the main risk factors and ambient meteorological variables., Results: A total of 4110 events were registered with a mild prevalence of MI (51.6%). In GLM analysis we observed a continuative association between CVD events and SO 2 (p<0.05), while PM 10 was associated with CVD occurrences at two-day lag time (p<0.05). Using GAM we observed a positive association between CVD and PM 10 at the same day and at three- and four-day lag time with HRs ranging between 1.025 and 1.039 (p<0.001). These results were observed for both MI and IS, with an earlier effect for MI than for IS., Conclusions: These data confirm a possible association between some ambient air pollutants and CVD events, precisely MI and IS, with different temporal and cumulative effect., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

The aim of this research is to evaluate the ability of transplanted lichen Pseudovernia (P). furfuracea to biomonitor and bioaccumulate in urban indoor environments. The elements As, Cd, Cr, Cu, Hg, Ni and Pb and 12 selected polycyclic aromatic hydrocarbons (PAHs) were used to assess P. furfuracea as a biomonitoring tool for the indoor air quality of school environments. To achieve this purpose, lichen samples were exposed for 2 months in the outdoor and indoor environments of five school settings located in urban and rural areas. The results demonstrated that transplanted lichen P. furfuracea is a suitable biomonitoring tool for metals and PAHs in indoor settings and can discriminate between different levels of air pollution related to urbanisation and indoor conditions, such as those characterised by school environments. A transplanted lichen biomonitoring strategy is cost-effective, "green", educational for attending children and less "invasive" than traditional air sampling methods. The feasibility of indoor monitoring by P. furfuracea is a relevant finding and could be a key tool to improve air quality monitoring programmes in school scenarios and thus focus on health prevention interventions for children, who are one of the most susceptible groups in the population.

This data article presents a dataset of mRNA levels for dopaminergic receptors, adrenoceptors and for tyrosine hydoxylase, the rate-limiting enzyme in the synthesis of catecholamines, in peripheral blood mononuclear cells as well as in CD4+ T effector and regulatory cells from subjects with clinically isolated syndromes (CIS), which is a first episode of neurological disturbance(s) suggestive of multiple sclerosis. CIS subjects are divided into two groups according to their eventual progression, after 12 months from CIS, to clinically established multiple sclerosis. The data reported are related to the article entitled "Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis" (M. Cosentino, M. Zaffaroni, M. Legnaro, R. Bombelli, L. Schembri, D. Baroncini, A. Bianchi, R. Clerici, M. Guidotti, P. Banfi, G. Bono, F. Marino, 2016) [1].

Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients. No information exists so far in CIS subjects. We investigated DR and AR gene expression in peripheral blood mononuclear cells (PBMC) and in CD4+ T effector (Teff) and regulatory (Treg) cells from CIS subjects, and assessed their relationship with MS progression after 12months. Expression of several DR and AR are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and α2A-AR mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12months. Results show the involvement of dopaminergic and adrenergic pathways in CIS as well as in MS pathogenesis, supporting the evaluation of dopaminergic and adrenergic agents in MS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The chemicals warfare agents (CWAs) are an extremely toxic class of molecules widely produced in many industrialized countries for decades, these compounds frequently contained arsenic. The plants where the CWAs have been produced or the plants where they have been demilitarized after the Second World War with unacceptable techniques can represent a serious environmental problem. CWAs standards are difficult to find on market so in present work an environmental assessment method based on markers has been proposed. Triphenylarsine, phenylarsine oxide and thiodiglycol have been selected as markers. Three reliable analytical methods based on gaschromatography and mass detection have been proposed and tested for quantitative analysis of markers. Methods performance have been evaluated testing uncertainty, linearity, recovery and detection limits and also comparing detection limits with exposure limits of reference CWAs. Proposed assessment methods have been applied to a case study of a former industrial plant sited in an area characterized by a high background of mineral arsenic.

Background and Purpose: Thrombolysis represents the best therapy for ischemic stroke but the main limitation of its administration is time. The avoidable delay is a concept reflecting the effectiveness of management pathway. For this reason, we projected a study concerning the detection of main delays with following introduction of corrective factors. In this paper we describe the results after these corrections., Materials and Methods: Consecutive patients admitted for ischemic stroke during a 3-months period to 35 hospitals of a macro-area of Northern Italy were enrolled. Each time of management was registered, identifying three main intervals: pre-hospital, in-hospital and total times. Previous corrective interventions were: 1.increasing of population awareness to use the Emergency Medical Service (EMS); 2.pre-notification of Emergency Department; 3.use of high urgency codes; 4.use of standardised operational algorithm. Statistical analysis was conducted using time-to-event analysis and Cox proportional hazard regression., Results: 1084 patients were enrolled. EMS was alerted for 56.3% of subjects, mainly in females and severe strokes (p<0.001). Thrombolytic treatment was performed in 4.7% of patients. Median pre-hospital and in-hospital times were 113 and 105min, while total time was 240. High urgency codes at transport contributed to reduce pre-hospital and in-hospital time (p<0.05). EMS use and high urgency codes promoted thrombolysis. Treatment within 4.5hours from symptom onset was performed in 14% of patients more than the first phase of study., Conclusions: The implementation of an organizational system based on EMS and concomitant high urgency codes use was effective to reduce avoidable delay and to increase thrombolysis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease, Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis., Results: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease., Conclusions: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series., (© 2016 American Heart Association, Inc.)

Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre-infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-κB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity.

The ability of a transplanted lichen, Pseudovernia (P.) furfuracea, to act as a multi-tracer biomonitoring tool for As, Cd, Ni, Pb, 12 PAHs, 17 polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and 27 polychlorinated biphenyls (PCBs) was evaluated at six areas of varying risk (high, medium, negligible) of pollutant fallout from a municipal waste incinerator in central Italy. Transplanted P. furfuracea proved to be an useful tool to biomonitor PCDDs/Fs and PCBs. Concentrations of As, heavy metals, PAHs, PCDDs/Fs resulted similar for all monitored stations. Small differences in total PCBs (4378 and 4631 pg/g dw vs 3298, 4123, 3676 and 4022 pg/g dw) and dioxin-like PCBs (1235 and 1265 pg/g dw vs 794, 1069, 1106 and 1188 pg/g dw) were observed. Air concentrations of monitored compounds appear to be more related to general air pollution than point emissions from the incinerator.