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Introduction/Objective: The KidneyIntelX is a multiplex, bioprognostic, immunoassay consisting of 3 plasma biomarkers and clinical variables that uses machine learning to predict a patient’s risk for a progressive decline in kidney function over 5 years. We report the 1-year pre- and post-test clinical impact on care management, eGFR slope, and A1C along with engagement of population health clinical pharmacists and patient coordinators to promote a program of sustainable kidney, metabolic, and cardiac health. Methods: The KidneyIntelX in vitro prognostic test was previously validated for patients with type 2 diabetes and diabetic kidney disease (DKD) to predict kidney function decline within 5 years was introduced into the RWE study (NCT04802395) across the Health System as part of a population health chronic disease management program from [November 2020 to April 2023]. Pre- and post-test patients with a minimum of 12 months of follow-up post KidneyIntelX were assessed across all aspects of the program. Results: A total of 5348 patients with DKD had a KidneyIntelX assay. The median age was 68 years old, 52% were female, 27% self-identified as Black, and 89% had hypertension. The median baseline eGFR was 62 ml/min/1.73 m 2 , urine albumin-creatinine ratio was 54 mg/g, and A1C was 7.3%. The KidneyIntelX risk level was low in 49%, intermediate in 40%, and high in 11% of cases. New prescriptions for SGLT2i, GLP-1 RA, or referral to a specialist were noted in 19%, 33%, and 43% among low-, intermediate-, and high-risk patients, respectively. The median A1C decreased from 8.2% pre-test to 7.5% post-test in the high-risk group ( P

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years. Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled. Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52. Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Abstract Bilinguals with a high proficiency in their first (L1) and second language (L2) often show comparable reaction times when switching from their L1 to L2 and vice-versa (“symmetrical switch costs”). However, the neurophysiological signatures supporting this effect are not well understood. Here, we ran two separate experiments and assessed behavioral and MEG responses in highly proficient Spanish-Basque bilinguals while they overtly name pictures in a mixed-language context. In the behavioral experiment, bilinguals were slower when naming items in switch relative to non-switch trials, and this switch cost was comparable for both languages (symmetrical). The MEG experiment mimicked the behavioral one, with switch trials showing more desynchronization than non-switch trials across languages (symmetric neural cost) in the alpha band (8–13 Hz). Source-localization revealed the engagement of right parietal and premotor areas, which have been linked to language selection and inhibitory control; and of the left anterior temporal lobe (ATL), a cross-linguistic region housing conceptual knowledge that generalizes across languages. Our results suggest that highly proficient bilinguals implement a language-independent mechanism, supported by alpha oscillations, which is involved in cue-based language selection and facilitates conceptually-driven lexical access in the ATL, possibly by inhibiting non-target lexical items or disinhibiting target ones.

Background and aim: Gut microbiota is considered as a complex organ of human body. The interaction between the host and microbiota is dynamic and controlled by a huge number of factors, such as lifestyle, geography, pharmaceuticals, diet, and stress. The breakdown of this relationship could change microbiota composition favoring the onset of several diseases, including cancer. Metabolites released by microbiota bacterial strains have been reported to elicit protective effects on the mucosa that could contrast cancer development and progression. Here, we tested the ability of specific probiotic strain Lactiplantibacillus plantarum OC01-derived metabolites (NCIMB 30624) to contrast the malignant features of colorectal cancer (CRC) cells. Experimental procedure: The study was performed on two cell lines, HCT116 and HT29, cultured in 2D and 3D, and focused on the hallmarks of cell proliferation and migration. Results and conclusion: Probiotic metabolites reduced cell proliferation both in 2D and 3D-spheroid cultures, the latter model mimicking the growth in vivo. The bacterial metabolites also contrasted the pro-growth and pro-migratory activity of inteurleukin-6 (IL-6), an inflammatory cytokine abundantly found in the tumor microenvironment of CRC. These effects were associated with inhibition of the ERK and of the mTOR/p70S6k pathways and with the inhibition of the E−to N-Cadherin switch. In a parallel study, we found that sodium butyrate (a representative of the main probiotic metabolites) induced autophagy and β-Catenin degradation, which is consistent with the growth inhibitory activity. The present data indicate that the metabolites of Lactiplantibacillus plantarum OC01 (NCIMB 30624) elicits anti-tumor effect and support its possible inclusion as adjuvant therapy of CRC for limiting cancer growth and progression.

The densely inhabited area of Naples (Italy), between the Campi Flegrei and Vesuvio volcanoes, is one of the most hazardous regions in the world. After two decades of sustained subsidence, Campi Flegrei has been experiencing an accelerating uplift since 2005. The uplift is currently associated with unusual seismicity and increased degassing. To try to identify the cause of the shift from subsidence to uplift and explore any connection between Campi Flegrei and Vesuvio, we analysed the ground displacement time series of the two volcanoes from 1993 to 2010, obtained from ERS/ENVISAT Synthetic Aperture Radar imagery. To distinguish between the various sources of deformation, we used simple scatter plots and a blind source separation technique called variational Bayesian independent component analysis (vbICA). We obtained consistent results using both approaches. Specifically, with vbICA, we identified two significant independent components (ICs). IC1 describes the subsidence that occurred at Campi Flegrei prior to 2000, including the mini-uplifts of 2000 and 2005, and part of the post-2005 uplift. The expansion and contraction of two volumes beneath Campi Flegrei satisfy IC1: a sill-shaped volume at a depth of approximately 3 km and a small volume at a depth of 1–2 km, respectively. The two sources of deformation reproduce the large-scale deformation in the Campi Flegrei area and the local deformation in the Solfatara area, respectively. In the Campi Flegrei area, IC2 exhibits primarily uplift, which is concentrated in the eastern part of the caldera. The deformation pattern is complex and difficult to interpret. If we model it using simple spheroidal deformation sources, the pattern suggests that two volumes at depths of approximately 9 and 8 km are experiencing opposite activity, namely contraction (beneath the southwestern part of the caldera) and expansion (beneath the central part of the caldera). In the Vesuvio area, IC2 is consistent with the deformation induced by the contraction of a volume at a depth of around 9 km. The contraction beneath Vesuvio is smaller in magnitude than the expansion/contraction beneath Campi Flegrei. The correlation observed after 2002 between uplift at Campi Flegrei and subsidence at Vesuvio suggests the transfer of magma and/or magmatic fluids between the two plumbing systems at 8–9 km depth. This implies that part of the ongoing unrest at Campi Flegrei may have been promoted by mass transfer from below Vesuvio.

Since the beginning of the COVID-19 pandemic, wastewater-based epidemiology (WBE) has been depicted as a promising environmental surveillance tool and early warning system. Predictive models for the estimate of COVID-19 cases from wastewater viral loads also earned lot of interest and are currently under development. Hereby a pilot study that compares WBE surveillance data with confirmed cases, total hospitalizations, doses of vaccine administered and predominance of coronavirus variants.Composite 24hrs wastewater samples were collected weekly between September 2021 and July 2022 from Padua wastewater treatment plant. Samples were processed following a previously published method. One-step RT-qPCR was performed for quantification, adapting an Orf1b-nsp14 gene assay. Variant replacement was derived from the monthly bulletins of the Italian National Health Institute. Aggregate data on vaccine doses administered and on COVID-19 prevalence and hospitalizations were retrieved from official reports.Eighty-two samples were processed. Viral loads highlighted 3 major peaks in January, April and July 2022. Quantitation of SARS-CoV-2 in wastewater and clinical surveillance resulted temporally juxtaposable. However, variation of the two curves is not proportional. SARS-CoV-2 showed its highest peak in April, whereas maximum COVID-19 prevalence was achieved in January. Total hospitalizations followed the prevalence trend. Omicron BA.1 started to replace the Delta variant in December 2021. Subsequently, the shift towards Omicron BA.2 occurred between February and April 2022. Finally, BA.4/5 attested around June, somehow preceding the summer peak.Emergence of Omicron BA.1 over Delta could be a possible driver of the increase in both clinical cases and wastewater viral load in January 2022. In late March 2022, Omicron BA.2 replaced BA.1: this reflected in a steep increase of wastewater viral load, but not of COVID-19 confirmed cases. When a dramatic drop in the testing capacity of clinical surveillance occurred, WBE was possibly capable of detecting a substantial increase in viral circulation.

European brown hare syndrome (EBHS) is a highly contagious and fatal viral disease, mainly affecting European brown hares (Lepus europaeus). The etiological agent, EBHS virus (EBHSV), belongs to the Lagovirus genus within the Caliciviridae family. The Italian hare (Lepus corsicanus) is endemic to Central-Southern Italy and Sicily and is classified as a vulnerable species. L. corsicanus is known to be susceptible to EBHS, but virological data available is scarce due to the few cases detected so far. In this study, we describe the occurrence of EBHS in two free-ranging L. corsicanus, found dead in a protected area of Central Italy. The two hares were identified as L. corsicanus using phenotypic criteria and confirmed through mitochondrial DNA analysis. Distinctive EBHS gross lesions were observed at necropsy and confirmed by subsequent histological examination. EBHSV was detected in the livers of the two animals initially using an antigen detection ELISA, followed by an EBHSV-specific reverse transcription-PCR, thus confirming the viral infection as the probable cause of death. The EBHS viruses detected in the two hares were identical, as based on blast analysis performed for the VP60 sequences and showed 98.86% nucleotide identity and 100% amino acid identity with strain EBHSV/GER-BY/EI97.L03477/2019, isolated in Germany in 2019. Phylogenetic analysis places our virus in group B, which includes strains that emerged after the mid-1980s. This study supports previous reports of EBHS in L. corsicanus and further expands the knowledge of the pathological and virological characteristics of the etiological agent. The ability of EBHSV to cause a fatal disease in the Italian hare represents a serious threat to the conservation of this vulnerable species, especially in populations kept in enclosed protected areas.

Abstract Surface structuring of topological insulator Bi2Te3 single crystals with femtosecond laser by varying pulses N and energy E is reported. Interesting effects related to laser‐induced periodic surface structures formation in this class of materials are evidenced. At low pulse energy, a clear formation of periodic, subwavelength ripples oriented orthogonally to the laser polarization is observed; those are restricted to an annular region surrounding a featureless central disk as the laser energy progressively increases. The structural analysis shows that some degree of crystallinity is preserved in the rippled area, but the central disk is amorphous resembling what is observed for germanium (Ge) and is associated with the hindering of surface structure formation due to a thick melted surface layer. Interestingly, at larger fluence or number of pulses, a transition to suprawavelength grooves occurs within the annular region covered by surface structures. The findings demonstrate a clear incubation behavior, suggesting that the formation of laser‐induced periodic surface structures is coherent with the general features of the process already reported for other materials. However, the disappearance of these structures in the central area, possibly resulting from the influence of the depth of the melt layer, indicates a mixed behavior for Bi2Te3.

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

IntroductionBrodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited.MethodsThe aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients’ demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded.ResultsAt week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab.ConclusionOur data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

Efficient and sustainable materials are requested to overcome the actual major issues related to green energy production. Ni/NiO nanoparticles (NPs, 2–4 nm in size) produced by Pulsed Laser Ablation in Liquid (PLAL) are reported as highly efficient and stable electrocatalysts for oxygen evolution reaction (OER) in water splitting applications. Ni/NiO NPs dispersions are obtained by ablating a Ni target immersed in deionized water with an Nd:YAG nanosecond pulsed laser. NPs size and density were driven by laser energy fluence (ranging from 8 to 10 J cm−2) and shown to have an impact on OER performance. Ni/NiO NPs were characterized by scanning and transmission electron microscopy, x-ray diffraction, photoemission spectroscopy, and Rutherford back-scattering spectrometry. By drop-casting onto graphene paper, anode electrodes were fabricated for electrochemical water splitting in alkaline electrolytes. The extrinsic and intrinsic catalytic performances for OER have been quantified, achieving an overpotential of 308 mV (at a current density of 10 mA cm−2) and unprecedented mass activity of more than 16 A mg−1, using NPs synthesized with the highest and lowest laser energy fluence, respectively. The impact of NPs’ size and density on OER performances has been clarified, opening the way for PLAL synthesis as a promising technique for highly efficient nano-electrocatalysts production.

Early research proposed that individuals with developmental dyslexia use contextual information to facilitate lexical access and compensate for phonological deficits. Yet at present there is no corroborating neuro-cognitive evidence. We explored this with a novel combination of magnetoencephalography (MEG), neural encoding and grey matter volume analyses. We analysed MEG data from 41 adult native Spanish speakers (14 with dyslexic symptoms) who passively listened to naturalistic sentences. We used multivariate Temporal Response Function analysis to capture online cortical tracking of both auditory (speech envelope) and contextual information. To compute contextual information tracking we used word-level Semantic Surprisal derived using a Transformer Neural Network language model. We related online information tracking to participants’ reading scores and grey matter volumes within the reading-linked cortical network. We found that right hemisphere envelope tracking was related to better phonological decoding (pseudoword reading) for both groups, with dyslexic readers performing worse overall at this task. Consistently, grey matter volume in the superior temporal and bilateral inferior frontal areas increased with better envelope tracking abilities. Critically, for dyslexic readers only, stronger Semantic Surprisal tracking in the right hemisphere was related to better word reading. These findings further support the notion of a speech envelope tracking deficit in dyslexia and provide novel evidence for top-down semantic compensatory mechanisms.

In the summer of 2017, huge wildfires in the British Columbia region (Canada) led to the injection of a remarkably high concentration of biomass burning aerosol in the atmosphere. These aerosol masses reached the city of Naples, Italy, at the end of August 2017, where they were characterized by means of a multiwavelength lidar and a sun–sky–lunar photometer. Here we report on the optical and microphysical properties of this aerosol in an intriguing condition, occurring on 4 September 2017, which is characterized by an interesting multi-layered vertical distribution of the aerosol. The Lidar profiles highlighted the presence of four aerosol layers, with two located in the lower troposphere and the other two at stratospheric altitudes. A rather thorough characterization of the biomass burning aerosol was carried out. The aerosol depolarization ratio showed an increasing dependence on the altitude with averaged values of 2–4% for the tropospheric layers, which are indicative of almost spherical smoke particles, and larger values in the stratospheric layers, suggestive of aspheric particles. Lidar-derived size distributions were retrieved for the first three aerosol layers, highlighting a higher particle concentration in the fine-mode fraction for the layers observed at higher altitudes. A dominance of fine particles in the atmosphere (fine-mode fraction > 0.8) with low absorption properties (absorption AOD < 0.0025 and SSA > 0.97) was also observed over the whole atmospheric column by sun photometer data. The space-resolved results provided by the lidar data are consistent with the columnar features retrieved by the AERONET sun photometer, thus evidencing the reliability and capability of lidar characterization of atmospheric aerosol in a very interesting condition of multiple aerosol layers originating from Canadian fires overpassing the observation station.

Methicillin-resistant biofilm-forming Staphylococcus spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly ineffective against multi-drug resistant bacteria. Moreover, they can induce dysbiosis, which favors opportunistic pathogen infections and alters immune responses. Consequently, research on pathogen containment strategies is crucial. We aimed to evaluate the potential beneficial effect of Lactobacillus johnsonii LJO02 cell-free supernatant (CFS) and vitamin D, as single treatments or in combination, on cell viability, wound healing, and the pro-inflammatory interleukin-6 (IL-6) production of a Staphylococcus aureus-infected human immortalized keratinocyte cell line (HaCaT) in vitro model. The analysis showed that LJO02 CFS 20% v/v ratio and 100 nM vitamin D promoted infected cell viability and wound healing and significantly reduced IL-6 production. However, their effect was not synergic, since no significant difference between the single and combined treatments was observed. LJO02 CFS topic application and vitamin D supplementation could provide a valuable strategy for attenuating S. aureus-induced pathogenesis, promoting wound healing and opening new therapeutic strategies supporting the conventional approaches.

Abstract Background Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting. Results Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp. Conclusions Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation. Video Abstract

Abstract The spread of multidrug-resistant bacteria, such as the skin commensal Staphylococcus aureus, is a worldwide health challenge; new methods to counteract opportunistic pathogen growth and virulence are urgent. We compared the activity of Lacticaseibacillus rhamnosus LR06 (DSM 21981) and Lactobacillus johnsonii LJO02 (DSM 33828) cell-free supernatants (CFSs) produced in the conventional animal derivative-based MRS medium and an innovative animal derivative-free broth (TIL) versus the MDR S. aureus (ATCC 43300). CFS influence was assessed towards the viability, metabolic activity, and ability to form biofilm of the MDR strain through optical density, alamarBlue assay, and crystal violet staining; their content in short-chain fatty acids, lactic acid, and proteins was analysed via high-resolution mass spectrometry and gas chromatography. All CFSs reduce viable and metabolically active S. aureus, being TIL more efficient compared to MRS in stimulating lactic acid bacteria metabolism and decreasing S. aureus biofilm formation. Particularly, the CFS from LJO02 grown in TIL has the best efficacy, revealing a high amount of lactic acid and 59 peculiar proteins; its effectiveness is partially maintained upon trypsin and proteinase K treatments, but not by pepsin and pH basification. Therefore, antagonistic CFSs may represent a strategic prevention approach, with bacteriotherapeutic and bio-repair potential.