Showing papers by "University of Modena and Reggio Emilia published in 2022"

<scp>VEXAS</scp> Syndrome: A Case Series From a <scp>Single‐Center</scp> Cohort of Italian Patients With Vasculitis

Abstract: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach.We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue.Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients.To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation.

Revisiting small-scale fluctuations in α-attractor models of inflation

Abstract: Abstract Cosmological α -attractors stand out as particularly compelling models to describe inflation in the very early universe, naturally meeting tight observational bounds from cosmic microwave background (CMB) experiments. We investigate α -attractor potentials in the presence of an inflection point, leading to enhanced curvature perturbations on small scales. We study both single- and multi-field models, driven by scalar fields living on a hyperbolic field space. In the single-field case, ultra-slow-roll dynamics at the inflection point is responsible for the growth of the power spectrum, while in the multi-field set-up we study the effect of geometrical destabilisation and non-geodesic motion in field space. The two mechanisms can in principle be distinguished through the spectral shape of the resulting scalar power spectrum on small scales. These enhanced scalar perturbations can lead to primordial black hole (PBH) production and second-order gravitational wave (GW) generation. Due to the existence of universal predictions in α -attractors, consistency with current CMB constraints on the large-scale spectral tilt implies that PBHs can only be produced with masses smaller than 10 8 g and are accompanied by ultra-high frequency GWs, with a peak expected to be at frequencies of order 10 kHz or above.

Characterization and Valorization of the Agricultural Waste Obtained from Lavandula Steam Distillation for Its Reuse in the Food and Pharmaceutical Fields

Abstract: The main focus of the current research was the characterization of the by-products from the steam distillation of Lavandula angustifolia Mill. (LA) and Lavandula x intermedia Emeric ex Loisel (LI) aerial parts, as they are important sources of bioactive compounds suitable for several applications in the food, cosmetic, and pharmaceutical industries. The oil-exhausted biomasses were extracted and the total polyphenol and flavonoid contents were, respectively, 19.22 ± 4.16 and 1.56 ± 0.21 mg/g for LA extract and 17.06 ± 3.31 and 1.41 ± 0.10 mg/g for LI extract. The qualitative analysis by liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS) revealed that both the extracts were rich in phenolic acids and glycosylated flavonoids. The extracts exhibited radical scavenging, chelating, reducing activities, and inhibitory capacities on acetylcholinesterase and tyrosinase. The IC50 values against acetylcholinesterase and tyrosinase were, respectively, 5.35 ± 0.47 and 5.26 ± 0.02 mg/mL for LA, and 6.67 ± 0.12 and 6.56 ± 0.16 mg/mL for LI extracts. In conclusion, the oil-exhausted biomasses demonstrated to represent important sources of bioactive compounds, suitable for several applications in the food, cosmetic, and pharmaceutical industries.

Ethical Constructivism

Abstract: Ethical constructivism holds that truths about the relation between rationality, morality, and agency are best understood as constructed by correct reasoning, rather than discovered or invented. Unlike other metaphors used in metaethics, construction brings to light the generative and dynamic dimension of practical reason. On the resultant picture, practical reasoning is not only productive but also self-transforming, and socially empowering. The main task of this volume is to illustrate how constructivism has substantially modified and expanded the agenda of metaethics by refocusing on rational agency and its constitutive principles. In particular, this volume identifies, compares and discusses the prospects and failures of the main strands of constructivism regarding the powers of reason in responding to the challenges of contingency. While Kantian, Humean, Aristotelian, and Hegelian theories sharply differ in their constructivist strategies, they provide compelling accounts of the rational articulation required for an inclusive and unified ethical community.

Relationship between weight gain and insulin resistance in people living with HIV switching to integrase strand transfer inhibitors-based regimens

Abstract: The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI.A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy.PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR.We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition.A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint that could be used in clinical and research settings.

Causality constraints on black holes beyond GR

Abstract: We derive causality constraints on the simplest scalar-tensor theories in which black holes differ from what General Relativity predicts, a scalar coupled to the Gauss-Bonnet or the Chern-Simons terms. Demanding that time advances are unobservable within the regime of validity of these effective field theories, we find their cutoff must be parametrically of the same size as the inverse Schwarzschild radius of the black holes for which the non-standard effects are of order one. For astrophysical black holes within the range of current gravitational wave detectors, this means a cutoff length at the km. We further explore the leading additional higher-dimensional operators potentially associated with the scale of UV completion and discuss their phenomenological implications for gravitational wave science.

Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease

Abstract: Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.

A simplified modelling of hydraulic fractures in elasto-plastic materials

Abstract: In this paper the problem of a plane strain hydraulic fracture propagating in an elasto-plastic material is analyzed. A new stress redistribution model for the proximity of the fracture tip is formulated and a resulting plasticity-dependent crack propagation condition is introduced. A modified variant of the KGD problem that accounts for the plastic deformations in the near-tip zone only is proposed. It is demonstrated that this model can be a credible substitute for the full elasto-plastic hydraulic fracture problem in the case of moderate plastic deformation. The crack-tip shielding effect introduced by the plastic deformation is quantified.

Nexus analysis and life cycle assessment of regional water supply systems: A case study from Italy

Abstract: Ensuring reliable access to water sources is an emerging issue being currently addressed by governments and international communities. However, local conditions play a primary role in determining requirements for urban water supply systems and cascade implications due to simultaneous interlinkages with complementary resources such as energy. As such, addressing sustainability in water management comes through quantitative evaluation modelling and assessment. To this aim, nexus analysis and life cycle assessment methodologies are applied to the drinking water supply system in the Romagna region (Italy). Our research provides detailed characterization of the involved material and energy flows, which is used as a basis for determining water-for-energy and energy-for-water results, and to conduct environmental assessment for complementary impact categories by withdrawal, treatment, and distribution processes. The results show that the energy needed to produce drinking water ranges from 0.27 MJ to 2.53 MJ per cubic meter of water delivered. Water deriving from the artificial basin and treated following a conventional technology turned out to be both the less energy intensive and the less impacting process. Overall, the study provides an exhaustive comparison of the environmental impacts of different water production alternatives, which may ultimately support decision-makers and local communities to the planning of strategies for optimized and long-term reliable access to water resources.

RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing

Abstract: Summary Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals' USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs' myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex DMD mutations due to a deep intronic variation and two large inversions, respectively. All three mutations affect DMD gene splicing and cause a lack of dystrophin protein production, and one of these also generates unique fusion genes and transcripts. Further characterization of USCs using a novel cell-sorting technology (Celector) highlighted cell-type variability and the representation of cell-specific DMD isoforms. Our comprehensive approach to USCs unraveled RNA, DNA, and cell-specific features and demonstrated that USCs are a robust tool for studying and diagnosing DMD.

From Undetectable Equals Untransmittable (U=U) to Breastfeeding: Is the Jump Short?

Abstract: Background: Vertical transmission of HIV infection may occur during pregnancy, at childbirth or through breastfeeding. Recommendations on the safety of breastfeeding of HIV-infected women on effective antiretroviral treatment are not univocal among international guidelines (WHO 2010, EACS 2017, DHHS 2017), leaving space for variability at the patient’s level. Methods: We collected clinical, laboratory and outcome data from 13 HIV-infected pregnant women who, between March 2017 and June 2021, elected to breastfeed their children against specific medical advice. All mothers were on antiretroviral therapy with darunavir or raltegravir plus emtricitabine/tenofovir disoproxil and remained HIV-RNA undetectable and >400 cells/mmc CD4+ lymphocytes during pregnancy and breastfeeding. Prophylactic antiretroviral therapy (zidovudine for 4 weeks) was started immediately after birth in all newborns. The mean duration of breastfeeding was 5.4 months. Newborns were tested for HIV-RNA multiple times: at birth, 1, 3, and 6 months after birth, and 1, 3 and 6 months after the end of breastfeeding. Results: None of the infants were infected by HIV. Conclusions: Our experience, gathered in the setting of freedom of choice on the patient’s side, while insufficient to address the eventual safety of breastfeeding in HIV-infected mothers since the represented cohort is numerically irrelevant, supports the extension of the U=U (Undetectable Equals Untransmittable) paradigm to this setting. Since breastfeeding is often requested by women with HIV planning pregnancy, more extensive comparative studies should be performed.