Tackling the Challenging Determination of Trace Elements in Ultrapure Silicon Carbide by LA-ICP-MS

The goal of accurately quantifying trace elements in ultrapure silicon carbide (SiC) with a purity target of 5N (99.999% purity) was addressed. The unsuitability of microwave-assisted acid digestion followed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was proved to depend mainly on the contamination induced by memory effects of PTFE microwave vessels and by the purity levels of acids, even if highly pure ones were used in a clean environment. A new analytical protocol for the direct analysis of the solid material by laser ablation coupled with ICP-MS (LA-ICP-MS) was then exploited. Different samples were studied; the best results were obtained by embedding SiC (powders or grains) in epoxy resin. This technique has the great advantage of avoiding any source of external contamination, as grinding, pressing and sintering pretreatments are totally unnecessary. Two different laser wavelengths (266 and 193 nm) were tested, and best results were obtained with the 266 nm laser. The optimized protocol allows the determination of elements down to the sub-mg/kg level with a good accuracy level

Global distribution and diversity of ovine-associated Staphylococcus aureus

Staphylococcus aureus is an important pathogen of many species, including sheep, and impacts on both human and animal health, animal welfare, and farm productivity. Here we present the widest global diversity study of ovine-associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA using multilocus sequence typing (MLST) and spa typing. These were compared with 196 sheep isolates from Europe (n = 153), Africa (n = 28), South America (n = 14) and Australia (n = 1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine isolates there were 22 STs and 37 spa types, including three novel MLST alleles, four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700) were detected in sheep and these contained 61% of all isolates. Four spa types (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main ovine CCs have different but overlapping patterns of geographical dissemination that appear to match the location and timing of sheep domestication and selection for meat and wool production. CC133, CC522 and CC700 remained ovine-associated following the inclusion of additional host species. Ovine isolates clustered separately from human and bovine isolates and those from sheep cheeses, but closely with caprine isolates. As with cattle isolates, patterns of clonal diversification of sheep isolates differ from humans, indicative of their relatively recent host-jump

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease

An organic neurophysiological tool for neuronal metabolic activity monitoring

Monitoring cell metabolism in vitro is considered a relevant methodology in several scientific fields ranging from fundamental biology research to neuro-toxicology. In the last 20 years, several in vitro neuro-pharmacological and neuro-toxicological approaches have been developed, with the intent of addressing the increasing demand for real-time, non-invasive in vitro systems capable of continuously and reliably monitoring cellular activity. In this paper, an Organic Charge Modulated Field Effect Transistor-based device is proposed as a promising tool for neuro-pharmacological applications, thanks to its ultra-high pH sensitivity and a simple fabrication technology. The preliminary characterization of this versatile organic device with primary neuronal cultures shows how these remarkable properties can be exploited for the realization of ultra-sensitive metabolic probes, which are both reference-less and low cost. These features, together with the already assessed capability of this sensor to also monitor the electrical activity of electrogenic cells, could provide important advances in the fabrication of multi-sensing lab-on-chip devices, thus opening up interesting perspectives in the neuro-pharmacological field

How to Clean and Safely Remove HF from Acid Digestion Solutions for Ultra-Trace Analysis: A Microwave-Assisted Vessel-Inside-Vessel Protocol

The complete dissolution of silicate-containing materials, often necessary for elemental determination, is generally performed by microwave-assisted digestion involving the forced use of hydrofluoric acid (HF). Although highly efficient in dissolving silicates, this acid exhibits many detrimental effects (e.g., formation of precipitates, corrosiveness to glassware) that make its removal after digestion essential. The displacement of HF is normally achieved by evaporation in open-vessel systems: atmospheric contamination or loss of analytes can occur when fuming-off HF owing to the non-ultraclean conditions necessarily adopted for safety reasons. This aspect strongly hinders determination at the ultra-trace level. To overcome this issue, we propose a clean and safe microwave-assisted procedure to induce the evaporative migration of HF inside a sealed “vessel-inside-vessel” system: up to 99.9% of HF can be removed by performing two additional microwave cycles after sample dissolution. HF migrates from the digestion solution to a scavenger (ultrapure H2O) via a simple physical mechanism, and then, it can be safely dismissed/recycled. The procedure was validated by a soil reference material (NIST 2710), and no external or cross-contamination was observed for the 27 trace elements studied. The results demonstrate the suitability of this protocol for ultra-trace analysis when the utilization of HF is mandatory

How to Clean and Safely Remove HF from Acid Digestion Solutions for Ultra-Trace Analysis: A Microwave-Assisted Vessel-Inside-Vessel Protocol

The complete dissolution of silicate-containing materials, often necessary for elemental determination, is generally performed by microwave-assisted digestion involving the forced use of hydrofluoric acid (HF). Although highly efficient in dissolving silicates, this acid exhibits many detrimental effects (e.g., formation of precipitates, corrosiveness to glassware) that make its removal after digestion essential. The displacement of HF is normally achieved by evaporation in open-vessel systems: atmospheric contamination or loss of analytes can occur when fuming-off HF owing to the non-ultraclean conditions necessarily adopted for safety reasons. This aspect strongly hinders determination at the ultra-trace level. To overcome this issue, we propose a clean and safe microwave-assisted procedure to induce the evaporative migration of HF inside a sealed “vessel-inside-vessel” system: up to 99.9% of HF can be removed by performing two additional microwave cycles after sample dissolution. HF migrates from the digestion solution to a scavenger (ultrapure H2O) via a simple physical mechanism, and then, it can be safely dismissed/recycled. The procedure was validated by a soil reference material (NIST 2710), and no external or cross-contamination was observed for the 27 trace elements studied. The results demonstrate the suitability of this protocol for ultra-trace analysis when the utilization of HF is mandatory.publishedVersio

Target alpha therapy with Thorium-227

Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (223Ra), the first-in-class a-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (227Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter 227Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies 227Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike 223Ra, the parent radionuclide 227Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of 227Th TAT in the treatment of several solid as well as hematologic malignancies