SARS-CoV-2 infection in cancer patients on active therapy after the booster dose of mRNA vaccines

The protective role against SARS-CoV-2 infection by the third booster dose of mRNA vaccines in cancer patients with solid malignancies is presently un- known. We prospectively investigated the occurrence of COVID-19 in cancer patients on active therapy after the booster vaccine dose. Methods: Cancer patients on treatment at the Center for Immuno-Oncology (CIO) of the University Hospital of Siena, Italy, and health care workers at CIO who had received a booster third dose of mRNA vaccine entered a systematic follow-up monitoring period to prospectively assess their potential risk of SARS-CoV-2 infection. Serological and microneu- tralization assay were utilized to assess levels of anti-spike IgG, and of neutralizing antibodies to the SARS-CoV-2 Wild Type, Delta and Omicron variants, respectively, after the booster dose and after negativization of the nasopharyngeal swab for those who had developed COV- ID-19. Results: Ninety cancer patients with solid tumors on active treatment (Cohort 1) and 30 health care workers (Cohort 2) underwent a booster third dose of mRNA vaccine. After the booster dose, the median value of anti-spike IgG was higher (p Z 0.009) in patients than in healthy subjects. Remarkably, 11/90 (12%) patients and 11/30 (37%) healthy subjects tested positive to SARS-CoV-2 infection during the monitoring period. Similar levels of anti-spike IgG and of neutralizing antibodies against all the investigated variants, with geometric mean titers of neutralizing antibodies against the Omicron being the lowest were detected after the booster dose and after COVID-19 in both Cohorts. Conclusions: The occurrence of SARS-CoV-2 infection we observed in a sizable proportion of booster-dosed cancer patients and in healthy subjects during the Omicron outbreak indicates that highly specific vaccines against SARS-CoV-2 variants are urgently required

Halophenol bioremediation catalyzed by an artificial peroxidase

Halophenols (HPs) have been widely used as pesticides, herbicides and wood-preserving agents. Once released into the environment, they exert toxic effects onto living systems such as plants, animals and humans.[1] Among bioremediation strategies targeting HPs, oxidative degradation is efficiently catalyzed by natural heme-enzymes, such as Horseradish Peroxidase (HRP),[2,3] in the presence of hydrogen peroxide as an oxidant. Peroxidases activate the phenol ring, by generating both phenoxy radical and carbocationic species, which further react to give coupling and/or oxidative dehalogenation products, such as chlorinated benzo-p-dioxins and quinones. The ability of these enzymes to cause phenolic coupling may allow the immobilization of toxic phenolic substances, such as HPs, limiting their bioavailability and suppressing their toxic effects. Humic acids (HA) are ubiquitous organic materials in terrestrial and aquatic ecosystems to which HPs can covalenty bind upon activation. In order to improve the chemical stability of natural peroxidases along with their catalytic efficiency, in recent years a variety of artificial biomimetic systems has been developed and evaluated to this purpose. [4] In this area, our ongoing project, focused on the design and synthesis of artificial enzymes led us to explore the activity of an artificial peroxidase, FeIII-Mimochrome VI*a (FeMC6*a), towards HPs.[5] Herein, the oxidative degradation of HPs catalyzed by FeMC6*a and its use in bioremediation strategies are reported. FeMC6*a is able to convert a variety of HPs, including 2,4,6-trichlorophenol (TCP) with 840-fold higher catalytic efficiency than natural HRP. 1. J. Huff, Chemosphere 2012, 89, 521. 2. S. Sumithran, M. Sono, G. M. Raner, J. H. Dawson, J. Inorg. Biochem. 2012, 117, 316. 3. K. Morimoto, K.Tatsumi, K-I Kuroda, Soil Biology & Biochemistry 2000, 32, 1071. 4. M. Chino, L. Leone, G. Zambrano, F. Pirro, D. D’Alonzo, V. Firpo, D. Aref, L. Lista, O. Maglio, F. Nastri, A. Lombardi, Biopolymers, 2018, e23107. 5. G. Caserta, M. Chino, V. Firpo, G. Zambrano, L. Leone, D. D’Alonzo, F. Nastri, O. Maglio, V. Pavone, A. Lombardi, ChemBioChem 2018, cbic.201800200

A biomimetic metalloporphyrin catalyzes indole oxidation with high selectivity

Indole is one of the most common heterocyclic scaffolds available in nature. It occurs in several natural compounds, including alkaloids, plant hormones, flower scents and dyes.1 Despite the structural simplicity of this molecule, indole oxidation commonly results in the formation of a large number of products, including the 2- or 3-oxygenated compounds, di-oxygenated and more complex molecules. For this reason, indole oxidation has become a widespread model reaction to test the efficacy of both biological catalysts2,3 and their synthetic analogues.4,5 Most of the catalysts examined so far gave poor selectivity toward any of the oxidation products.2-5 Here we present the results concerning oxidation of indole and its derivatives catalyzed by Mn-Mimochrome VI*a (Mn-MC6*a). Mn-MC6*a is a synthetic peptide-porphyrin conjugate conceived to act as a miniaturized heme-protein model.6 Mn-MC6*a is able to oxidize indole under unprecedented site-selective conditions, yielding to 3-oxindolenine as single product. Additionally, the reaction selectivity is dramatically altered when 1- or 3-methyl-substituted indoles are used as substrates. The formation and isolation of the reactive 3-oxindolenine is highly important, since it is believed to represent a useful synthon in organic synthesis. Accordingly, the exploitation of its reactivity with nucleophiles, in order to provide one pot transformations, is currently ongoing, with the aim to further increase the synthetic potential of our catalyst. 1. Burton, T.C. in Heterocyclic scaffolds II: Reactions and applications of indoles; Gribble, G.W., Ed.; Springer-Verlag Berlin Heidelberg, 2011. 2. Kuo, H. H. and Mauk, A. G.; Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 13966–13971. 3. Barrios, D. A. et al. J. Am. Chem. Soc. 2014, 136, 7914-7925. 4. Linhares, M. et al. Appl. Catal. A. 2014, 470, 427–433. 5. Poon L. C.-H. et al. J. Am. Chem. Soc. 2011, 133, 1877–1884. 6. Caserta, G. et al. ChemBioChem 2018 (doi: 10.1002/cbic.201800200

Selective Oxidation of Halophenols Catalyzed by an Artificial Miniaturized Peroxidase

The development of artificial enzymes for application in sustainable technologies, such as the transformation of environmental pollutants or biomass, is one of the most challenging goals in metalloenzyme design. In this work, we describe the oxidation of mono-, di-, tri- and penta-halogenated phenols catalyzed by the artificial metalloenzyme Fe-MC6*a. It promoted the dehalogenation of 4-fluorophenol into the corresponding 1,4-benzoquinone, while under the same experimental conditions, 4-chloro, 4-bromo and 4-iodophenol were selectively converted into higher molecular weight compounds. Analysis of the 4-chlorophenol oxidation products clarified that oligomers based on C-O bonds were exclusively formed in this case. All results show that Fe-MC6*a holds intriguing enzymatic properties, as it catalyzes halophenol oxidation with substrate-dependent chemoselectivity

Integration of proprioception in upper limb prostheses through non-invasive strategies: a review

Abstract Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another

Factors associated with clinical and radiological status on admission in patients with aneurysmal subarachnoid hemorrhage

Grading scales yield objective measure of the severity of aneurysmal subarachnoid hemorrhage and serve as to guide treatment decisions and for prognostication. The purpose of this cohort study was to determine what factors govern a patient's disease-specific admission scores in a representative Central European cohort. The Swiss Study of Subarachnoid Hemorrhage includes anonymized data from all tertiary referral centers serving subarachnoid hemorrhage patients in Switzerland. The 2009-2014 dataset was used to evaluate the impact of patient and aneurysm characteristics on the patients' status at admission using descriptive and multivariate regression analysis. The primary/co-primary endpoints were the GCS and the WFNS grade. The secondary endpoints were the Fisher grade, the presence of a thick cisternal or ventricular clot, the presence of a new focal neurological deficit or cranial nerve palsy, and the patient's intubation status. In our cohort of 1787 consecutive patients, increasing patient age by 10 years and low pre-ictal functional status (mRS 3-5) were inversely correlated with "high" GCS score (GCS ≥ 13) (OR 0.91, 95% CI 0.84-0.97 and OR 0.67, 95% CI 0.31-1.46), "low" WFNS grade (grade VI-V) (OR 1.21, 95% CI 1.04-1.20 and OR 1.47, 95% CI 0.66-3.27), and high Fisher grade (grade III-IV) (OR 1.08, 95% CI 1.00-1.17 and OR 1.54, 95% CI 0.55-4.32). Other independent predictors for the patients' clinical and radiological condition at admission were the ruptured aneurysms' location and its size. In sum, chronological age and pre-ictal functional status, as well as the ruptured aneurysm's location and size, determine the patients' clinical and radiological condition at admission to the tertiary referral hospital

Additional file 1 of Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP)

Additional file 1: Supplementary Table 1. Web-based Questionnaire [original language]

Additional file 8 of Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP)

Additional file 8: Supplementary Table 8. Long-term outcomes identified among patients with cyclic vomiting syndrome according to specific outpatient clinic