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Abstract Background Botulism is a rare and life-threatening disease caused by the potent botulinum neurotoxin (BoNT), which can be produced by Clostridium botulinum (C. botulinum) and related bacteria. Clinical manifestations, which include a symmetrical, descending muscular paralysis, generalized hypotonia, and potentially respiratory failure, are non-specific and diagnosis is challenging, especially when anamnesis does not reveal any typical risk factor, like honey consumption. Case Presentation We present what is, to the best of our knowledge, the first documented case of infant botulism (IB) in Sicily and discuss its peculiarities and the challenges faced in the diagnostic-therapeutic process. The infant was exclusively breastfed and no history of consumption of possibly contaminated foods, like honey, was found. The signs observed at presentation included poor suction, hypotonia, and hyporeactivity. A detailed anamnesis motivated the suspicion of botulism, due to the occurrence of constipation and exposure to dust from home renovation works during the days before the onset of symptoms. The botulinum antitoxin was administered and the diagnosis was confirmed through fecal examination, detecting toxin-producing C. botulinum. Conclusion IB should be considered in every infant with rapidly progressing hypotonia and a history of constipation. However rarely, transmission could occur through inhalation of dust particles containing the toxin, therefore it is important to explore all possible sources of exposure. In the case described, timely diagnosis and treatment determined the successful outcome, which highlights the importance of early intervention in managing IB.

The effectiveness of Volterra equalization (VE) is analyzed to improve the performance of a metropolitan area network (MAN), characterized by directly-modulated (DM) vertical-cavity surface-emitting laser (VCSEL) sources combined with coherent detection, in order to target both high capacity and hundreds of km reaches. VE, which is a well-known nonlinear equalization technique, is used to cope not only with the distortion introduced by the real implementation of direct discrete multi-tone (DMT) modulation of the VCSEL, but also with the nonlinear impairments. A suitable experimentation, in case of 25-GHz spaced dense wavelength division multiplexed (DWDM) propagation, allows to validate a simulation tool, developed to provide a systematic analysis of the supported capacity per VCSEL, with and without VE. Simulations permit to analyze the effects of VE for different channel spacings (25, 50 and $100\,$ GHz) and for different standard single-mode fiber (SSMF) lengths (up to $200\,$ km), focusing on the evolution of the capacity per channel in case of different launch powers and optical signal-to-noise ratios. The dependence of the VE effectiveness is evaluated also in terms of spectral behavior. VE allows to achieve up to 13%-capacity increase, assuring 50 Gb/s rate per polarization per VCSEL, in case of DWDM transmission and after 200-km propagation, as targeted by the considered MAN applications.

Abstract Designing metal sites into de novo proteins has significantly improved, recently. However, identifying the minimal coordination spheres, able to encompass the necessary information for metal binding and activity, still represents a great challenge, today. Here, we test our understanding with a benchmark, nevertheless difficult, case. We assemble into a miniature 28-residue protein, the quintessential elements required to fold properly around a FeCys4 redox center, and to function efficiently in electron-transfer. This study addresses a challenge in de novo protein design, as it reports the crystal structure of a designed tetra-thiolate metal-binding protein in sub-Å agreement with the intended design. This allows us to well correlate structure to spectroscopic and electrochemical properties. Given its high reduction potential compared to natural and designed FeCys4-containing proteins, we exploit it as terminal electron acceptor of a fully artificial chain triggered by visible light.

Abstract Here, we show that in a supramolecular system with more than 20 building blocks forming large icosahedral M 12 L 8 metal–organic cages (MOCs), using the instant synthesis method, it is possible to kinetically trap and control the formation of interlocking M 12 L 8 nanocages, giving rare M 12 L 8 TPB-ZnI2 poly-[n]-catenane. The catenanes are obtained in a one-pot reaction, selectively as amorphous (a1) or crystalline states, as demonstrated by powder X-ray diffraction (powder XRD), thermogravimetric (TG) analysis and 1H NMR. The 300 K M 12 L 8 poly-[n]-catenane single crystal X-ray diffraction (SC-XRD) structure including nitrobenzene (1) indicates strong guest binding with the large M 12 L 8 cage (i.e., internal volume ca. 2600 Å3), allowing its structural resolution. Conversely, slow self-assembly (5 days) leads to a mixture of the M 12 L 8 poly-[n]-catenane and a new TPB-ZnI2 (2) coordination polymer (i.e., thermodynamic product), as revealed by SC-XRD. The neat grinding solid-state synthesis also yields amorphous M 12 L 8 poly-[n]-catenane (a1′), but not coordination polymers, selectively in 15 min. The dynamic behavior of the M 12 L 8 poly-[n]-catenanes demonstrated by the amorphous-to-crystalline transformation upon the uptake of ortho-, meta- and para-xylenes shows the potential of M 12 L 8 poly-[n]-catenanes as functional materials in molecular separation. Finally, combining SC-XRD of 1 and DFT calculations specific for the solid-state, the role of the guests in the stability of the 1D chains of M 12 L 8 nanocages is reported. Energy interactions such as interaction energies (E), lattice energies (E*), host–guest energies (E host-guest ) and guest-guest energies (E guest-guest ) were analysed considering the X-ray structure with and without the nitrobenzene guest. Not only the synthetic control achieved in the synthesis of the M 12 L 8 MOCs but also their dynamic behavior either in the crystalline or amorphous phase are sufficient to raise scientific interest in areas ranging from fundamental to applied sides of chemistry and material sciences.

Nel suo scritto intitolato What is moving right now? Elton Marques cerca di rispondere alla domanda su cosa sia la spotlight cui si riferisce la teoria temporale detta Moving Spotlight Theory ed espone l’idea che si tratti del flusso di coscienza relativo ai nostri stati mentali. Dopo aver presentato la sua tesi, introduco un’ipotesi aggiuntiva allo scopo di risolvere una difficoltà presente nella sua interpretazione. Benché Marques non tenti di sostenere il modello della MST rispetto ad altri modelli temporali, egli cerca di rendere la sua ipotesi convincente. Per questo motivo, io stesso metto qui a confronto il modello della MST (in particolare nella versione offerta da Marques) con altri modelli temporali, per valutarne la plausibilità all’interno del dibattito complessivo riguardante le principali teorie sul tempo, che pertanto vengono esposte nelle loro linee essenziali.

The cytochrome P450 family consists of ubiquitous monooxygenases with the potential to perform a wide variety of catalytic applications. Among the members of this family, CYP116B5hd shows a very prominent resistance to peracid damage, a property that makes it a promising tool for fine chemical synthesis using the peroxide shunt. In this meticulous study, we use hyperfine spectroscopy with a multifrequency approach (X- and Q-band) to characterize in detail the electronic structure of the heme iron of CYP116B5hd in the resting state, which provides structural details about its active site. The hyperfine dipole–dipole interaction between the electron and proton nuclear spins allows for the locating of two different protons from the coordinated water and a beta proton from the cysteine axial ligand of heme iron with respect to the magnetic axes centered on the iron. Additionally, since new anti-cancer therapies target the inhibition of P450s, here we use the CYP116B5hd system—imidazole as a model for studying cytochrome P450 inhibition by an azo compound. The effects of the inhibition of protein by imidazole in the active-site geometry and electron spin distribution are presented. The binding of imidazole to CYP116B5hd results in an imidazole–nitrogen axial coordination and a low-spin heme FeIII. HYSCORE experiments were used to detect the hyperfine interactions. The combined interpretation of the gyromagnetic tensor and the hyperfine and quadrupole tensors of magnetic nuclei coupled to the iron electron spin allowed us to obtain a precise picture of the active-site geometry, including the orientation of the semi-occupied orbitals and magnetic axes, which coincide with the porphyrin N-Fe-N axes. The electronic structure of the iron does not seem to be affected by imidazole binding. Two different possible coordination geometries of the axial imidazole were observed. The angles between gx (coinciding with one of the N-Fe-N axes) and the projection of the imidazole plane on the heme were determined to be −60° and −25° for each of the two possibilities via measurement of the hyperfine structure of the axially coordinated 14N.

This paper studies the secrecy capacity of an n-dimensional Gaussian wiretap channel under a peak power constraint. This work determines the largest peak power constraint R¯n, such that an input distribution uniformly distributed on a single sphere is optimal; this regime is termed the low-amplitude regime. The asymptotic value of R¯n as n goes to infinity is completely characterized as a function of noise variance at both receivers. Moreover, the secrecy capacity is also characterized in a form amenable to computation. Several numerical examples are provided, such as the example of the secrecy-capacity-achieving distribution beyond the low-amplitude regime. Furthermore, for the scalar case (n=1), we show that the secrecy-capacity-achieving input distribution is discrete with finitely many points at most at the order of R2σ12, where σ12 is the variance of the Gaussian noise over the legitimate channel.

This paper documents the dataset obtained from the Electron Paramagnetic Resonance (EPR) study of the electronic properties of a self-sufficient cytochrome P450, CYP116B5hd, which possesses an interesting catalytic activity for synthetic purposes. In fact, when isolated, its heme domain can act as a peroxygenase on different substrates of biotechnological interest.Raw data shown in Famulari et al. (2022) and supplementary data in raw and processed forms (figures) are documented and available in this paper. Additionally, simulations of the experimental data together with simulation scripts based for EasySpin, a widespread MATLAB toolbox for EPR spectral simulations, are provided. The procedure for g-value analysis based on a crystal-field theory is also detailed here, offering an interesting tool for comparison of FeIII-heme P450 systems.Due to the catalytic interest of the protein, which has been recently discovered, and the correlation that has been reported between g-values and peroxidase function, both, CW-EPR and HYSCORE spectra and data set of the model CYPBM3hd are also provided.Finally, the materials and methods for enzyme production and purification, sample preparation and experimental and spectroscopic procedures a together with instrumental details are described in detail.The data files and simulation scripts can be found in: https://doi.org/10.5281/zenodo.6418626

In September 2021, the La Fossa crater at Vulcano, in Italy, entered a new phase of unrest. We discuss a set of monitoring parameters included in the INGV surveillance network, which closely tracked the sequence of effects related to the crisis. The low-frequency local seismicity sharply increased, while the GPS and tiltmeter networks recorded the inflation of the cone, as an effect of fluid expansion in the hydrothermal system. Gravity variations were probably the effects of fast processes within shallow sources. The anomalies in soil CO2 flux, fumarole temperature, and in plume SO2 flux marked the strong increase in the vapor output from crater fumaroles. The signs of the impending crisis had been evident in the chemical and isotopic composition of fumarole gases since July 2021. These geochemical anomalies were clearly indicative of the enhanced input of gases from a magmatic source. In October, the massive degassing also influenced the areas at the base of the cone. In some areas, soil CO2 degassing and the thermal aquifer recorded strong anomalies. By early November, the crisis reached its acme. Afterward, the monitored parameters started a slow and discontinuous decreasing trend although remaining, some of them, sensibly above the background for several months. The multidisciplinary approach proved decisive for the interpretation of the underlying processes acting in the different phases of the unrest, thus allowing a consistent evaluation of the multiple hazards.

Introduction: Infertile couples' percentage is increasing all over the world, especially in Italy, with high number of children born in our country through assisted reproductive techniques (ART). However, pregnancies obtained by ART have increased potential obstetrical risks which could be caused by fetus-placenta unit development, most of all due to placentation's evolution. These can be reassumed into miscarriage, chromosomal abnormalities, preterm delivery, multiple pregnancy, IUGR, placenta previa, abruptio placentae, preeclampsia and hypertensive disorders, postpartum hemorrhage., Methods: The aim of this article is to evaluate hypothetic mechanism involved in placentation process and in the etiopathology of ART pregnancies disorders, giving an updating overview of different etiopathogenetic pathways and features. On this scenario, we create an updated review about the etiopathogenesis of abnormal placentation in ART pregnancies., Results: Several features and different etiopathogenetic characteristic might impact differently such as advanced maternal age, poor ovarian reserve, oocyte quality and causes of subfertility themselves, and the ART techniques itself, as hormonal medical treatments and laboratory techniques such as gamete and embryo laboratory culture, cryopreservation versus fresh ET, number of embryos transferred., Conclusion: To further explore the molecular mechanisms behind placentation in ART pregnancies, further studies are necessary to gain a better understanding of the various aspects involved, particularly those which are not fully comprehended. This could prove beneficial to clinicians in both ART care and obstetric care, as it could help to stratify obstetrical risk and decrease complications in women undergoing ART, as well as perinatal disorders in their children. Correct placentation is essential for a successful pregnancy for both mother and baby., 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 © 2024 Elsevier B.V. All rights reserved.)

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients.

(1) Background: Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor with excellent activity against the multidrug-resistant (MDR) P. aeruginosa . Continuous infusion (CI) dosing allows the optimization of pharmacokinetic and pharmacodynamic (PK/PD) properties of β-lactam antibiotics and may support patients' treatment as outpatients. (2) Methods: Adult patients receiving their entire course of C/T as a CI in the outpatient setting were retrospectively included in the study. The primary outcome evaluated was clinical resolution. The secondary outcomes evaluated were PK/PD target attainment (ƒT > 4 × MIC) and microbiologic clearance at the end of treatment. Therapeutic drug monitoring to assess C/T concentration was performed. (3) Results: Three patients were enrolled in the study and received 9 g of C/T in CI every 24 h. One patient received an additional course of antimicrobial therapy due to disease exacerbation six months after initial treatment, accounting for four evaluated treatments. The primary outcome was achieved in 3/4 treatments and the secondary outcome was achieved in 4/4 and 3/3, respectively. In all patients, free ceftolozane concentrations were >10 times higher than the EUCAST breakpoint (4 mg/L). (4) Conclusions: Elastomeric infusion of C/T delivered in CI can be an effective and convenient way to treat acute diseases caused by MDR- P. aeruginosa , avoid hospital admission, and contribute to infection control strategies. Despite the small number of enrolled patients, clinical and microbiological results support this strategy.