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Backgroud: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. Aim: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. Methods: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. Conclusion: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported.

Finding a therapy for ischemia-reperfusion injury, which consists of cell death following restoration of blood flowing into the artery affected by ischemia, is a strong medical need. Nowadays, only the use of broad-spectrum molecular therapies has demonstrated a partial efficacy in protecting the organs following reperfusion, while randomized clinical trials focused on more specific drug targets have failed. In order to overcome this problem, we applied a combination of molecular modeling and chemical synthesis to identify novel spiropiperidine-based structures active in mitochondrial permeability transition pore opening inhibition as a key process to enhance cell survival after blood flow restoration. Our results were confirmed by biological assay on an in vitro cell model on HeLa and human renal proximal tubular epithelial cells and pave the way to further investigation on an in vivo model system.

Hadronic matrix elements involving tensor currents play an important r\^ole in decays that allow to probe the consistency of the Standard Model via precision lattice QCD calculations. The non-singlet tensor current is a scale-dependent (anomalous) quantity. We fully resolve its renormalisation group (RG) running in the continuum by carrying out a recursive finite-size scaling technique. In this way ambiguities due to a perturbative RG running and matching to lattice data at low energies are eliminated. We provide the total renormalisation factor at a hadronic scale of 233 MeV, which converts the bare current into its RG-invariant form. Our calculation features three flavours of O(a) improved Wilson fermions and tree-level Symanzik-improved gauge action. We employ the (massless) Schr\"odinger functional renormalisation scheme throughout and present the first non-perturbative determination of the Symanzik counterterm $c_\mathrm{T}$ derived from an axial Ward identity. We elaborate on various details of our calculations, including two different renormalisation conditions., Comment: 39 pages, 10 figures, 11 tables

We present a lattice QCD determination of light quark masses with three sea-quark flavours (Nf= 2 + 1). Bare quark masses are known from PCAC relations in the framework of CLS lattice computations with a non-perturbatively improved Wilson-Clover action and a tree-level Symanzik improved gauge action. They are fully non-perturbatively improved, including the recently computed Symanzik counter-term bA- bP. The mass renormalisation at hadronic scales and the renormalisation group running over a wide range of scales are known non-perturbatively in the Schrödinger functional scheme. In the present paper we perform detailed extrapolations to the physical point, obtaining (for the four-flavour theory) mu/d(2GeV)=3.54(12)(9)MeV and ms(2GeV)=95.7(2.5)(2.4)MeV in the MS ̄ scheme. For the mass ratio we have ms/ mu / d= 27.0 (1.0) (0.4). The RGI values in the three-flavour theory are Mu/d=4.70(15)(12)MeV and Ms=127.0(3.1)(3.2)MeV.

Introduction: Haemophilia management and patients’ quality of life significantly improved. However, data on current patients’, caregivers’ and clinicians’ satisfaction and limitations of treatments and haemophilia management are limited. Aim: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. Methods: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. Conclusions: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.

We report on our ongoing determination of the charm quark mass and the masses and decay constants of various charmed mesons, obtained within a mixed-action setup. We employ $N_f=2+1$ CLS ensembles combined with a Wilson twisted mass valence action that eliminates the leading $O(a)$ effects from our target observables. Alongside our preliminary results, we will discuss an exploration of GEVP techniques aimed at optimizing the precision in view of the extension of the computation to heavier quark masses. We study the chiral-continuum extrapolation of decay constants for charm quark observables and the renormalized charm quark mass., Comment: Proceedings of the 38th International Symposium on Lattice Field Theory, LATTICE2021 26th-30th July, 2021, Zoom/Gather@Massachusetts Institute of Technology

We report on our ongoing determination of the charm quark mass and the masses and decay constants of various charmed mesons, obtained within a mixed-action setup. We employ $N_f=2+1$ CLS ensembles combined with a Wilson twisted mass valence action that eliminates the leading $O(a)$ effects from our target observables. Alongside our preliminary results, we will discuss an exploration of GEVP techniques aimed at optimizing the precision in view of the extension of the computation to heavier quark masses. We study the chiral-continuum extrapolation of decay constants for charm quark observables and the renormalized charm quark mass., Comment: Proceedings of the 38th International Symposium on Lattice Field Theory, LATTICE2021 26th-30th July, 2021, Zoom/Gather@Massachusetts Institute of Technology

We report on our ongoing determination of the charm quark mass and the masses and decay constants of various charmed mesons, obtained within a mixed-action setup. We employ $N_f=2+1$ CLS ensembles combined with a Wilson twisted mass valence action that eliminates the leading $O(a)$ effects from our target observables. Alongside our preliminary results, we will discuss an exploration of GEVP techniques aimed at optimizing the precision in view of the extension of the computation to heavier quark masses. We study the chiral-continuum extrapolation of decay constants for charm quark observables and the renormalized charm quark mass., Comment: Proceedings of the 38th International Symposium on Lattice Field Theory, LATTICE2021 26th-30th July, 2021, Zoom/Gather@Massachusetts Institute of Technology

The nociceptin/orphanin FQ (N/OFQ)/N/OFQ receptor (NOP) system controls different biological functions including pain and cough reflex. Mixed NOP/opioid receptor agonists elicit similar effects to strong opioids but with reduced side effects. In this work, 31 peptides with the general sequence [Tyr/Dmt1,Xaa5]N/OFQ(1-13)-NH2 were synthesized and pharmacologically characterized for their action at human recombinant NOP/opioid receptors. The best results in terms of NOP versus mu opioid receptor potency were obtained by substituting both Tyr1 and Thr5 at the N-terminal portion of N/OFQ(1-13)-NH2 with the noncanonical amino acid Dmt. [Dmt1,5]N/OFQ(1-13)-NH2 has been identified as the most potent dual NOP/mu receptor peptide agonist so far described. Experimental data have been complemented by in silico studies to shed light on the molecular mechanisms by which the peptide binds the active form of the mu receptor. Finally, the compound exerted antitussive effects in an in vivo model of cough.

We present a lattice QCD determination of light quark masses with three sea-quark flavours (Nf=2+1). Bare quark masses are known from PCAC relations in the framework of CLS lattice computations with a non-perturbatively improved Wilson-Clover action and a tree-level Symanzik improved gauge action. They are fully non-perturbatively improved, including the recently computed Symanzik counter-term bA−bP. The mass renormalisation at hadronic scales and the renormalisation group running over a wide range of scales are known non-perturbatively in the Schrödinger functional scheme. In the present paper we perform detailed extrapolations to the physical point, obtaining (for the four-flavour theory) mu/d(2 GeV)=3.54(12)(9) MeV and ms(2 GeV)=95.7(2.5)(2.4) MeV in the MS¯ scheme. For the mass ratio we have ms/mu/d=27.0(1.0)(0.4). The RGI values in the three-flavour theory are Mu/d=4.70(15)(12) MeV and Ms=127.0(3.1)(3.2) MeV.

We present a nearly final analysis of the $u/d$ and $s$ quark masses, extracted using the PCAC quark masses reported in [PRD 95 (2017) 074504]. The data is based on the CLS $N_f = 2 + 1$ simulations with Wilson/Clover quarks and L\"uscher-Weisz gauge action, at four $\beta$ values (i.e. lattice spacings) and a range of quark masses. We use the ALPHA results of [EPJC 78 (2018) 387] for non-perturbative quark mass renormalisation and RG-running from hadronic to electroweak scales in the Schr\"odinger Functional scheme. Quark masses are quoted both in the $\overline{\rm MS}$ scheme and as RGI quantities., Comment: Talk presented at the 36th Annual International Symposium on Lattice Field Theory (Lattice 2018), 22-28 July 2018, Michigan, USA

We present a nearly final analysis of the $u/d$ and $s$ quark masses, extracted using the PCAC quark masses reported in [PRD 95 (2017) 074504]. The data is based on the CLS $N_f = 2 + 1$ simulations with Wilson/Clover quarks and L\"uscher-Weisz gauge action, at four $\beta$ values (i.e. lattice spacings) and a range of quark masses. We use the ALPHA results of [EPJC 78 (2018) 387] for non-perturbative quark mass renormalisation and RG-running from hadronic to electroweak scales in the Schr\"odinger Functional scheme. Quark masses are quoted both in the $\overline{\rm MS}$ scheme and as RGI quantities., Comment: Talk presented at the 36th Annual International Symposium on Lattice Field Theory (Lattice 2018), 22-28 July 2018, Michigan, USA

We present a nearly final analysis of the $u/d$ and $s$ quark masses, extracted using the PCAC quark masses reported in [PRD 95 (2017) 074504]. The data is based on the CLS $N_f = 2 + 1$ simulations with Wilson/Clover quarks and L\"uscher-Weisz gauge action, at four $\beta$ values (i.e. lattice spacings) and a range of quark masses. We use the ALPHA results of [EPJC 78 (2018) 387] for non-perturbative quark mass renormalisation and RG-running from hadronic to electroweak scales in the Schr\"odinger Functional scheme. Quark masses are quoted both in the $\overline{\rm MS}$ scheme and as RGI quantities., Comment: Talk presented at the 36th Annual International Symposium on Lattice Field Theory (Lattice 2018), 22-28 July 2018, Michigan, USA

We determine from first principles the quark mass anomalous dimension in Nf=3 QCD between the electroweak and hadronic scales. This allows for a fully non-perturbative connection of the perturbative and non-perturbative regimes of the Standard Model in the hadronic sector. The computation is carried out to high accuracy, employing massless O (a) -improved Wilson quarks and finite-size scaling techniques. We also provide the matching factors required in the renormalisation of light quark masses from lattice computations with O (a) -improved Wilson fermions and a tree-level Symanzik improved gauge action. The total uncertainty due to renormalisation and running in the determination of light quark masses in the SM is thus reduced to about 1% .

We present the current status of a revised strategy to compute the running of renormalized quark masses in QCD with three flavours of massless O(a) improved Wilson quarks. The strategy employed uses the standard finite-size scaling method in the Schr\"odinger functional and accommodates for the non-perturbative scheme-switch which becomes necessary at intermediate renormalized couplings as discussed in [arXiv:1411.7648]., Comment: 7 pages, 3 figures, 1 table; Proceedings of the 33rd International Symposium on Lattice Field Theory, 14-18 July 2015, Kobe, Japan

We present the current status of a revised strategy to compute the running of renormalized quark masses in QCD with three flavours of massless O(a) improved Wilson quarks. The strategy employed uses the standard finite-size scaling method in the Schr\"odinger functional and accommodates for the non-perturbative scheme-switch which becomes necessary at intermediate renormalized couplings as discussed in [arXiv:1411.7648]., Comment: 7 pages, 3 figures, 1 table; Proceedings of the 33rd International Symposium on Lattice Field Theory, 14-18 July 2015, Kobe, Japan

We present the current status of a revised strategy to compute the running of renormalized quark masses in QCD with three flavours of massless O(a) improved Wilson quarks. The strategy employed uses the standard finite-size scaling method in the Schr\"odinger functional and accommodates for the non-perturbative scheme-switch which becomes necessary at intermediate renormalized couplings as discussed in [arXiv:1411.7648]., Comment: 7 pages, 3 figures, 1 table; Proceedings of the 33rd International Symposium on Lattice Field Theory, 14-18 July 2015, Kobe, Japan