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Objective: The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi. Method: A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs. Results: The cohort comprised 1434 patients. The mean age was 53.8years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate. Conclusions: Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.

BackgroundIn real-life setting, a greater number of elderly rheumatoid arthritis (RA) patients with impaired glomerular filtration rate (GFR) needs treatment with biologic or target synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) to achieve disease control and reduce NSAIDs intake. Long-term observational data from the real-life on the use of b/tsDMARD in these patients are scarce.ObjectivesThe aim of this study was to evaluate the retention rate of b/tsDMARD in RA patients with impaired GFR in real-life setting.MethodsData of RA patients treated with at least one b/tsDMARD were retrospectively analyzed form the national Italian GISEA registry from January 2016 to December 2021. Estimated-GFR (eGFR) was calculated with the Cockcroft-Gault equation at the time of any b/tsDMARD prescription. For the purpose of this study, patients were divided in two groups, patients with impaired GFR (eGFR ≤60) and patients with normal GFR (eGFR >60). The retention rate was calculated by the Kaplan-Meier method and compared between these two groups by a log-rank test.ResultsThe study population included 2443 treatment-line with b/tsDMARD from 1888 patients (female 80.4%, age 57±12 years, mean baseline CDAI 17±12, FR/ACPA+ 69.5%) who started a new b/tsDMARD. Disease characteristics are shown in Table 1. 288 treatments with b/tsDMARD were started in patients with impaired eGFR and 2155 in patients with normal eGFR. Compared to patients with eGFR >60, patients with eGFR ≤60 showed higher HAQ-DI (1.3±0.8 vs 1±0.8, pConclusionOur data show that impaired eGFR seems to not influence the persistence of b/tsDMARD treatment in RA patients.Disclosure of InterestsNone declared

BackgroundIn May 2020, the executive committee of the Italian Society of Rheumatology (SIR) endorsed the Italian study group (SG) on capillaroscopy and microcirculation in rheumatic diseases (CAPSIR) that first convened at the virtual annual meeting the same year. Nowadays capillaroscopy is a well-established, non-invasive technique with useful clinical applications in the assessment of connective tissue diseases (CTDs) [1] and mandatory for the differential diagnosis of Raynaud’s phenomenon (Rp) [2]. Despite growing interest in the use of this imaging technique in clinical and research settings, data on its current usage to assess microcirculation in rheumatic diseases in Italy are not available.ObjectivesTo obtain an insight into the current utilization of capillaroscopy in the assessment of rheumatic patients in the Italian clinical setting.This survey aimed: 1) to obtain an overview on the usage of capillaroscopy in rheumatological clinical practice in Italy, and 2) to gauge expert’s attitudes on factors influencing its use and the potential critical issues.MethodsThis online survey was devised to evaluate the opinions of the members of the SIR about nailfold capillaroscopy. It was designed with the contributions of the steering committee of CAPSIR SG, and emails with a link to the survey were sent to physicians affiliated with the SIR between July and August 2021 on behalf of the CAPSIR SG. At the beginning of the survey, the physician most experienced in capillaroscopy was asked to complete the questionnaire on behalf of his/her center. Questions were about the use of this technique in clinical practice and its critical issues. Data were reported with a descriptive analysis.ResultsOne hundred and one centers, with at least one representative for each of the twenty Italian Region, completed the survey. 51.5% of respondents were in non-university hospitals, and 70 (69.3%) centers perform more than 100 capillaroscopy per year. The respondents were mainly practicing capillaroscopy for more than 5 years (85%) and gained certification of national or international dedicated training courses (84%). 43% of respondents had at least one scientific publication on this topic. Videocapillaroscope with 200X magnification was the most used instrument (91%). In public health services, the waiting time to schedule capillaroscopy is less than 3 months in 62.4% of centers. The survey has identified attitudes toward the use of capillaroscopy in the assessment and management of CTDs. In the screening phase of Rp, it is performed every 12 (mean value) months in patients with antinuclear antibodies (ANA) negative and every 6 months for those with positive ANA. Capillaroscopy is performed every 12 months (mean value) as part of the staging of CTDs (including systemic sclerosis). In more than 60% of centers, there is no specific diagnostic program for the screening of Rp and there is no connection with the general practitioners. 70% of the centers use capillaroscopy to follow the effect of therapies at least in systemic sclerosis.ConclusionAt least one center for each Italian Region participated in this national survey, thus ensuring good geographical coverage. Moreover, the personnel who perform the exam had certified training and experience thus supporting the reliability of results. This survey indicates that the Italian public health system allows an acceptable waiting time to schedule the exam (less than 3 months). Italian Rheumatologists prescribe capillaroscopy as part of the clinical routine in the screening of Rp and as part of the annual checkup of CTDs. Critical issues remain the lack of a specific program and network with the general practitioners. To have a wider vision on this topic, our survey could be further extended to other European countries.References[1]Cutolo M, Smith V. Detection of microvascular changes in systemic sclerosis. and other rheumatic diseases. Nat Rev Rheumatol 2021;17(11):665-677.[2]van den Hoogen F, Khanna D, et al. 2013 classification criteria for systemic sclerosis: an ACR/EULAR collaborative initiative. Ann Rheum Dis 2013;72(11):1747-55.Disclosure of InterestsNone declared

BackgroundMixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterized by heterogeneous clinical manifestations mainly involving skin, kidney and peripheral nervous system.Despite reassuring safety data from EULAR Coronavirus Vaccine (COVAX) physician-reported registry, a significant proportion of patients with autoimmune diseases reported unwillingness to get vaccinated against SARS-CoV-2 infection in the preliminary results of the COVAD study, due to concerns about the lack of long-term safety data, and fear of associated side effects and disease flare.ObjectivesAims of this multicentre Italian study were to investigate the prevalence of vaccination against SARS-CoV-2 in Italian population of MCV patients, to explore the reason for the missed vaccination, and to investigate short and long-term side effects of the vaccine, including vasculitis flare.MethodsAll MCV patients referring to 12 Italian centres were investigated about vaccination and possible both short- (within 48 hours) and long-term (within 30 days) adverse events (AE), classified according to FDA Toxicity Grading Scale for preventive vaccine clinical trials, and possible disease flares. Patients with MCV related to lymphoproliferative disorders or connective tissue diseases were excluded from the study.The baseline variables were expressed as percentages or mean±standard deviation. The differences between continuous variables were analysed using the Mann–Whitney nonparametric test. The chi-squared test, or Fischer’s exact when appropriate, were used for categorical variables (absolute numbers and percentages) regarding baseline characteristics.ResultsA total of 416 patients, 69.2% females and 30.8% males, with a mean age of 70.4±11.7 years, were included in the study.Only 7.7% of patients were not vaccinated, mainly for fear of adverse events (50%) or for medical decision (18.8%). Corminaty was the vaccine most frequently used (80.5%). Interestingly, 6 patients (1.44%) were with a heterologous vaccination (usually AstraZeneca-Corminaty).Considering ongoing treatment, not vaccinated subjects were more frequently treated with chronic glucocorticoid therapy and/or Rituximab (p=0.049 and p=0.043 respectively).AE were recorded in 31.7% of cases, mainly mild and self-limiting (grade 1). More severe adverse events, such as flare of vasculitis, were observed in 5.3% of cases.AE were not associated with the kind of vaccine used and with the clinical manifestations of vasculitis. Patients with active MCV showed a lower frequency of short-term (within 48 hours) adverse events, but patients affected by peripheral neuropathies or skin vasculitis frequently showed a flare of their symptoms, recorded in 40% and 25% of cases, respectively. Finally, patients under glucocorticoid treatment were more prone to develop a vasculitis flare within a month after vaccination.ConclusionVaccination in MCV patients has been performed in a high percentage of patients showing a good safety. Other than patients’ fear, treatments with rituximab and glucocorticoids are the main reasons for delaying vaccination, and it should be considered by the physician before starting therapy. Vasculitis flares were observed in about 5% of cases, in line with that observed in other autoimmune diseases. Specific attention should be reserved to people with purpura or peripheral neuropathy, for the increased risk of exacerbation of their symptoms.References[1]Visentini M et al Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2 2021[2]Machado PM et al Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine COVAX physician-reported registry 2021[3]Sen P et al COVAD Study Group. COVID-19 vaccination in autoimmune disease COVAD survey protocol 2022[4]Scarpato S et al Italian Group for the Study of Cryoglobulinaemia GISC. Provisional recommendations for SARS-CoV-2 vaccination in patients with cryoglobulinaemic vasculitis 2021Disclosure of InterestsNone declared

Aquest article proposa un model d’avaluació de les competències socials des de l’àrea d’Educació Física. Per a la seva elaboració s’utilitza un disseny observacional nomotètic (diversos participants que executen una mateixa tasca), de seguiment (diferents patrons de conductes observades durant mesos) i multidimensional (diverses dimensions que es corresponen amb els criteris de l’instrument d’observació), amb la creació d’una eina ad hoc validada per experts. D’aquest disseny se’n deriven una sèrie de decisions sobre els participants, els instruments d’observació, de registre i el procediment d’anàlisi. S’utilitza l’anàlisi seqüencial de retards, prospectius i retrospectius, per obtenir les taules seqüencials que generen les discussions i l’anàlisi de resultats. L’anàlisi seqüencial posa en relació conductes obtingudes diacrònicament i busca patrons de repetició en el temps. D’altra banda, l’anàlisi seqüencial de retards es complementa amb la utilització de la tècnica de coordenades polars que permet obtenir un mapa complet de les interrelacions entre les diferents categories de les diverses dimensions. La característica més destacada de la recerca és la utilització del programa HOISAN 1.6.3 (Hernández-Mendo et alii, 2012), que permet, per primer cop, calcular de manera informatitzada l’anàlisi de coordenades polars. A partir de l’eina ad hoc i dels resultats obtinguts s’elabora la proposta de model d’avaluació de les competències socials de l’àrea d’Educació Física.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD.

L’arribada d’Internet, de les xarxes socials digitals, de les aplicacions mòbils i la constant evolució de les TIC (Tecnologies de la Informació i la Comunicació) i les TAC (Tecnologies de l’Aprenentatge i el Coneixement) demanen d’una adaptació als nous contextos a l’àmbit de l’educació.La incorporació de dispositius mòbils, l’ús d’aplicacions educatives i la participació en diferents tipus de xarxes, ja siguin socials digitals o no, afavoreixen el treball col·laboratiu, la recerca d’informació en diferents àmbits i formats, i la incorporació de noves maneres d’aprendre i de relacionar-se.L’àrea d’educació física ha de poder aprofitar aquest nou paradigma educatiu per millorar els processos d’ensenyament i d’aprenentatge del professorat i de l’alumnat amb criteris de varietat, innovació per poder-ne promocionar la pròpia activitat física i esportiva i fer-ne un hàbit per a tota la vida, a la vegada que es desenvolupa la competència digital de tots els protagonistes del procés educatiu.

Background:Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed.Objectives:We aimed to evaluate the association of antecedent MTX use with development of RA-ILD.Methods:Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.Results:Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; PConclusion:Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD.Disclosure of Interests:Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodríguez Henríquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramcés Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoît Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Lioté: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphaël Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieudé: None declared

De la mateixa manera que cal prendre cons­ciència que no podem seguir llençant plàstics indiscriminadament i impune, o que hem d’aturar les emissions de CO2 per no malmetre el medi ambient i perjudicar les espècies que hi ­viuen fent perillar la seva existència i el futur del planeta, ens cal conscienciar que tots en som responsables.

Professional and personal competencies are valid indicators to evaluate productive and human processes. Competencies are also a reference for the development of individuals, groups and organisations that are developed before and during the professional working commitments. This article discusses the main concepts related to the emotional competencies of a tennis coach and stresses their importance in daily work.

In the last decade, research efforts on the investigation of MgO/SiO2 cements have significantly grown because they are one of the most promising materials for the encapsulation of radioactive waste.(1-4) In the presence of water, MgO/SiO2 mixtures hydrate and form a binder phase, M-S-H (magnesium silicate hydrate), a colloidal gel analogue to calcium silicate hydrate (C-S-H), present in traditional cements. Even if research interest in MgO-based cement is growing, only one additive has been used so far with this kind of cement, while in CaO-based cement many additives are commonly used to modulate the performances to specific applications. It has been recently reported that sodium hexametaphosphate in MgO-based cements increases the fluidity of the pastes, which is essential for practical applications, but its action mechanism is still unknown.(5-7) In this study we investigated the mechanism of interaction of different phosphate-based salts with MgO-based cements, in order to understand the structural changes induced by phosphate presence on the hydration reaction and on the M-S-H structure. We evaluated the effect of adding sodium orthophosphate (OP), sodium trimetaphosphate (TMP) and sodium hexametaphosphate (HMP), in comparison with a sample without additive. The effect of the investigated additives on M-S-H has been studied with a multi-technique approach: the kinetics of hydration of the studied pastes were monitored by means of differential scanning calorimetry, the hydrated phases formed during the reaction have been characterized by thermogravimetric analysis, infrared spectroscopy, X-ray diffraction and solid state NMR. The morphology and topography of the pastes have been studied by scanning electron microscopy and atomic force microscopy. Moreover, we performed a characterization of the mechanical properties by statistical nanoindentation and Vickers micro-indentation. The results evidenced that phosphate salts influence the hydration reaction, which is more efficient especially in presence of sodium ortophosphate that enhances M-S-H precipitation even more than the currently used additive sodium hexametaphosphate. References: 1. M. Schneider, et al., Cem. Concr. Res., 2011, 41, 642. 2. E. M. Gartner and D. E. Macphee, Cem. Concr. Res., 2011, 41, 736. 3. S. A. Walling et al., Dalton Trans., 2015, 44, 8126. 4. F. Jin and A. Al-Tabbaa, Cem. Concr. Compos., 2014, 52, 27. 5. Z. Li et al., Constr. Build. Mater., 2014, 61, 252-259. 6. T. Zhang et al., Cem. Concr. Res., 2014, 65, 8-14. 7. Y. Jia et al., Cem. Concr. Res., 2016, 89, 63-71. Acknowledgements: CSGI and FIR2013 (Project RBFR132WSM) for financial support.

Various kinds of fumed silica nanoparticles, different in terms of specific surface area and surface functionalization, were melt compounded with a poly(lactic acid) biodegradable matrix, with the aim to investigate the thermo-mechanical and optical properties of the resulting materials. Untreated nanoparticles at elevated surface area resulted to be effective in increasing elastic modulus, because of the extended filler–matrix interaction, while the finer dispersion of silica aggregates at the nanoscale obtained with surface treated nanoparticles led to noticeable improvements of the tensile properties at yield and at break, both under quasi-static and impact conditions. Also the fracture toughness and the creep stability were substantially enhanced by nanosilica addition, without impairing the original optical transparency of the matrix.

Recommendations for activity after obstetric and gynecologic procedures remain based on tradition and anecdote. After reviewing the current evidence base, guidelines, and practice for postdischarge instructions related to physical activity after the most common obstetric and gynecologic surgical procedures, we conclude that the available data do not support many of the recommendations currently provided. Restrictions on lifting and climbing stairs should likely be abandoned. Guidance on driving should focus on the concern regarding cognitive function and analgesics rather than concerns of wound separation/dehiscence. Given the impact of these recommendations on daily life events, consistent, evidence-based advice on when and how women can safely resume exercise, driving, working, and sexual intercourse is critical. The evidence base informing advice for most of these issues is minimal; we need prospective, well-designed studies to help guide us and our patients.

Relapsing polychondritis is a rare immune-mediated condition, characterized by episodic inflammation of the cartilaginous tissue, in particular the ears, nose, and eyes, and involvement of joints and respiratory tract. Nearly one third of patients showed other associated diseases, such as systemic vasculitides, connective tissue diseases, or myelodysplastic syndromes. Antiphospholipid antibodies can be found in relapsing polychondritis in patients with no clinical thrombotic disease. However, when antiphospholipid syndrome is present, its clinical manifestations can be severe and life threatening. We describe the case of a patient with relapsing polychondritis associated to Budd-Chiari syndrome due to antiphospholipid syndrome. The present clinical observations together with the updated review of the literature suggest a search for antiphospholipid antibodies in all patients with relapsing polychondritis.

A numerical study was carried out by finite element analysis (FEA) for the calculation of absolute values and through-thickness variation of residual stress originating in thermal spray coatings. The investigated deposit was an air plasma sprayed alumina coating sprayed on a carbon steel substrate previously coated with Ni20Al bond coat. Results show compressive residual in-plane stresses with linear through-thickness variation and tensile normal and shear stresses having a peak at the coating-substrate interface. The influence of deposition temperature on residual stress was also investigated. The experimental validation of the FEA model was carried out using a high-speed hole drilling technique, suitably adapted for the analysis of a multimaterial structure through FEA calculation of the required calibration coefficients. A very good agreement between simulated and measured stresses was obtained, inspite of the adopted simplification hypothesis.

Parallel to the democratisation process of Spain which took place during the political transition (1975-1982), there were major changes in the status of sports in the country, in both the different administrations’ positions and in the reality of this phenomenon. This study focuses on analysing some of the most noteworthy initiatives in the neighbourhood and educational movements to promote school sports in the city of Barcelona during this period, as well as the role played by the administrations, particularly after 1979. Methodologically, this study has taken a hermeneutic approach via the analysis of primary and secondary sources. The actions of these agents helped to diminish the sport deficit which existed after the Franco dictatorship (1939-1975) through initiatives such as creating sports clubs at schools, the School Sports Council of Barcelona and sports introduction schools.

Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase γ ( POLG1 ) are associated with a range of clinical syndromes characterized by secondary mtDNA defects, including mtDNA depletion and multiple mtDNA deletions.1 The phenotypic spectrum of POLG1 -associated disease ranges from fatal childhood encephalopathy with intractable epilepsy and liver failure (Alpers-Huttenlocher syndrome)2 to late-onset clinical disease affecting a single organ (for a review, see reference 3). We describe a fatal skeletal and visceral myopathy in the neonatal period associated with recessive POLG1 mutations. ### Case report. A newborn boy of healthy nonconsanguineous parents was delivered at 37 weeks’ gestation by cesarean section. His mother (primipara, 32 years old) had been admitted to our hospital 2 weeks previously because of reduced fetal intrauterine movements and polyhydramnios. The child’s birthweight was 2,330 g (

Premessa: Nonostante una generale giustificabilità sul piano etico, la sedazione palliativa (SP) presenta ancora numerosi aspetti controversi che richiedono un ulteriore dibattito e chiarificazione. Dal punto di vista pratico, inoltre, si osserva una notevole variabilità per quanto riguarda la procedura clinica della SP e un confine tra la SP alla fine della vita e l’eutanasia involontaria sempre più sottile e incerto. Questa situazione rende particolarmente necessaria l’elaborazione di percorsi decisionali trasparenti, anche nella forma di linee-guida locali, che chiariscano le procedure e le implicazioni etiche della sedazione palliativa. Obiettivi: Lo scopo di questo lavoro è di presentare le principali caratteristiche del percorso decisionale e assistenziale per la SP elaborato presso il Policlinico Universitario “Campus Bio-Medico” di Roma. Metodi: L’elaborazione della proposta presentata è stata preceduta da uno studio, attraverso la somministrazione di questionari semistrutturati, sulle conoscenze del personale medico e infermieristico in merito alla SP e da uno studio retrospettivo sulle cartelle cliniche, per verificare le modalità di utilizzo della SP all’interno dell’ospedale. Risultati: Il percorso decisionale ed assistenziale elaborato considera non solo gli aspetti farmacologici, ma affronta con chiarezza anche le implicazioni etiche e legali della procedura di SP, e in particolare la comunicazione, la cura dei familiari e degli operatori sanitari, la possibilità di avvalersi della consulenza di etica clinica nei casi più complessi o nei quali è difficile raggiungere una decisione condivisa. Si sottolinea, inoltre, come l’applicazione di un percorso decisionale e assistenziale per la SP debba essere supportata da momenti formativi e di confronto attivo tra gli operatori sanitari, per favorire l’adeguata comprensione e il corretto utilizzo di tali strumenti operativi, ma anche per assicurare il rispetto della coscienza degli operatori sanitari coinvolti. Conclusioni: È raccomandabile che tutte le istituzioni sanitarie producano percorsi decisionali ed assistenziali per la SP, attenti non solo agli standard scientifici, ma anche alla sensibilità etica e culturale del contesto in cui verranno utilizzate. Percorsi decisionali ed assistenziali così strutturati forniscono non solo un orientamento operativo e formativo per l’agire clinico, ma costituiscono anche un doveroso strumento di trasparenza nei confronti dei pazienti, dei loro familiari, della stessa struttura sanitaria e di tutta la società. ---------- Background: Despite a general ethical basis for justification, palliative sedation (PS) still has many controversial aspects that require further discussion and clarification. From a practical standpoint, moreover, there is considerable variability in the clinical procedure and an increasingly uncertain boundary between PS and involuntary euthanasia. This situation makes it necessary to develop local guidelines to clarify the procedures and the ethical implications of PS. Purpose: The aim of this paper is to present the main features of the ethical and clinical decision-making process for PS developed at the University Hospital “Campus Bio-Medico”, in Rome. Methods: The development of the present proposal was preceded by a survey, through a questionnaire, on the knowledge of medical and nursing staff on PS, and a retrospective study on medical records, to see how PS is used inside the hospital. Results: The benefit of this decision-making process is that it considers the pharmacological aspects, but also clearly addresses the ethical and legal procedure of PS, communication, the care for family members and health workers, the possibility of taking advantage of a clinical ethics consultation in complex cases or where it is difficult to reach a joint decision. We also emphasize that the application of the decision-making process must be supported by training sessions and active confrontation, to promote proper understanding and correct use of the guidelines themselves, but also to ensure respect for the conscience of health care professionals who are involved in the procedures of PS. Conclusions: It is recommended that all health care institutions produce local guidelines for PS, attentive to scientific standards, but also sensitive to the ethical and cultural context in which they are used. Ethical and clinical guidelines provide not only a well-structured operational guidance and training for clinical work, but are also a necessary tool for transparency with regard to all society.

Il presente lavoro ha l’obiettivo di condividere con la comunità scientifica, le riflessioni sorte all’interno di un Gruppo di Lavoro sul tema delle Cure Palliative costituito nell’Ospedale S. Giovanni Calibita dell’Isola Tiberina di Roma. Ci si è chiesti: come si muore in Ospedale? Che attenzione c’è nei confronti del paziente non guarito e destinato al trapasso in termini medio brevi? Le cure palliative possono essere di ausilio in questa fase di assistenza? Come modificare le abitudini consacrate di un ospedale per acuti e come indirizzare le stesse verso una maggior attenzione al problema delle cure di fine vita? E poi: il supporto palliativo deve restare destinato a coprire solo le ultime fasi della vita o intervenire anche prima? Lo stato dell’arte dimostra quanto ancora sia lontano lo sviluppo di una corretta mentalità di approccio al tema in discussione in ambiente ospedaliero e, fatto salve alcune virtuose eccezioni, ancora tende a distinguersi la fase puramente interventistica dell’azione sulla malattia da quella più attenta al controllo dei sintomi posticipata ad un momento successivo e distinto dall’intervento causale. Molto resta da fare in ambito ospedaliero ed il pensiero comune tra i componenti del gruppo è che solo attraverso una adeguata formazione, si può orientare la preparazione del personale verso una cultura diversa che permetta di guardare al paziente nella sua interezza ampliando la prospettiva che fa sì che ci si occupi solo della sua malattia. L’articolo riporta le riflessioni dei componenti del gruppo di lavoro rappresentanti di diverse unità operative e di vari servizi trasversali i quali, con oggettività e trasparenza, propongono una lettura critica dell’attenzione al tema delle cure palliative nelle unità operative di appartenenza. ---------- This work aims to share with the scientific community, the reflections arising within a Working Group on Palliative Care in Tiber Island Hospital – S. John Calibita – in Rome. The questions were: How people die in the hospital? What’s the approach to the patient not healed but nearly to die? Can palliative care be an aid in this fase of assistance? How can we change legitimate routines and modifying them to the issue of end of life care in acute-care hospitals? Can palliative support be intended only in the last stages of life or intervene before? The state of the art is far away from the development of a correct approach regarding palliative care in hospitals and except for a certain exceptions, it still tends to stand out on the stage of the disease interventional purely than the most careful control of symptoms. From the point of view of the group much remains to be done in the hospital especially aiming, with proper training, a different culture that allows to look at the patient as a whole and not just the disease. The article reflects the opinion of the working group who represents the different Operative Units and Cross-Services in our hospital. They propose a critical “reading” about palliative care according to their personal experience.

Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms.

The use of Molybdenum is of interest in various technological areas. Because of its remarkable properties (high melting point (2610°C), high conductivity, good chemical stability and high hardness), Mo coatings have been used in microelectronics (gates for MOS integrated circuits, interconnections, and diffusion barriers), as back contacts for solar cells and they are suitable candidates to fabricate superconducting microcalorimeters for high-performance radiation detectors. Moreover Molybdenum films are used in nuclear energy applications and for missile and aircraft parts. As a consequence of their appeal, a variety of deposition techniques and conditions has been employed to obtain Mo coatings.Nonetheless, a detailed study of the process-structure-properties for Mo-based coatings is still lacking in the literature.In this work, we present an investigation, based on the use of high resolution characterization methodologies, on the properties of Mo deposited by sputtering on titanium substrates. Different films have been grown under different sputtering conditions to find a correlation between a variety of deposition parameters and the intrinsic properties of the films. The working gas has been also changed (Ar, Xe, etc.) to evaluate its influence on the growing layer. Microstructural characterization activities consisted of scanning electron microscopy (SEM), X-ray diffraction (XRD) and focused ion beam (FIB) cross section analysis. The residual stress distribution was investigated by using an innovative high resolution focused ion beam micro-ring-core method. The nano-mechanical properties of the films (hardness and modulus) were analyzed by nanoindentation testing. Wear resistance and adhesion were finally analyzed by means of scratch and tribological tests, using a fully-computerized UMT tester. Results showed a significant modification of coatings' microstructure, depending on the adopted working gas and process parameters. In particular, a transition from a micro-crystalline columnar microstructure to a nano-porous microstructure was observed by using different kind of working gas. Modifications of the residual stress field and mechanical properties were also observed, as a function of the process parameters, and a correlation with observed adhesion and wear resistance is proposed.

This double-blind randomized study of 116 healthy women was undertaken to evaluate whether alkalinization potentiated the analgesic effects of epidural fentanyl-lidocaine for elective Caesarean section. After a test-dose of 3 ml, lidocaine 2% with adrenaline 1:200,000, all patients received 100 micrograms, fentanyl in 5 ml saline and they were then divided into two groups, to receive incremental doses of 5 ml lidocaine 2% with adrenaline 1:200,000 with or without 0.1 mEq.ml-1 sodium bicarbonate, to obtain anaesthesia to T4. The addition of bicarbonate to lidocaine resulted in a mean (SD) pH increase from 6.58 (0.01) to 7.14 (0.02) and in a mean PCO2 increase from 3.8 (0.8) to 345.1 (5.9) mmHg. Onset of sensory analgesia to the S1 segment as well as the interval between the block and the delivery of the baby were shorter in the bicarbonate group (respectively 15.4 (6.9) vs 18.9 (4.8) min and 28.9 (9.5) versus 33.9 (11.8) min; P < 0.01 and 0.05). No differences were noted in the onset to T4 or in the degree of motor block. The percentage of patients experiencing pain during surgery and requiring intravenous analgesics was higher in the group which did not receive bicarbonate (3% vs 16%; P < 0.05). There were no differences in intraoperative maternal side-effects, neonatal outcome or in maternal venous and umbilical venous and arterial lidocaine concentrations between the groups. The concentrations of fentanyl in maternal plasma, umbilical artery, and the umbilical artery to maternal vein ratio were greater in the alkalinized group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Many patients chronically infected by hepatitis C virus (HCV) experience symptoms like fatigue, dyspnea and reduced physical activity. However, in many patients, these symptoms are not proportional to the liver involvement and could resemble symptoms of chronic heart failure. To our knowledge, no study evaluated serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in a large series of patients with HCV chronic infection (HCV+). Serum NT-proBNP was assayed in 50 patients HCV+ and in 50 sex- and age-matched controls. HCV+ patients showed significantly higher mean NT-proBNP level than controls (P = 0.001). By defining high NT-proBNP level as a value higher than 125 pg/mL (the single cut-off point for patient under 75 years of age), 34% HCV+ and 6% controls had high NT-proBNP (Fisher exact test; P0.001). With a cut-off point of 300 pg/mL (used to rule out chronic heart failure in patients under 75 years of age) 10% HCV+ and 0 controls had high NT-proBNP (Fisher exact test; P = 0.056). With a cut-off point of 900 pg/mL (used for ruling in chronic heart failure in patients with age 50-75) 8% HCV+ patients and 0 controls had high NT-proBNP (Fisher exact test; P = 0.12). The study demonstrates high levels of circulating NT-proBNP in HCV+ patients compared to healthy controls. The increase of NT-proBNP may indicate the presence of a sub-clinical cardiac dysfunction. Further prospective studies quantifying these symptoms in correlation with echocardiography are needed to confirm this association.

In this work, we compare experimental measured density of defects in amorphous silicon‐carbon alloys with a theoretical expression obtained by applying a thermodynamic equilibrium defects model to the intrinsic defect concentration in the semiconductor. The samples were deposited under different conditions of hydrogen dilutions and two substrate temperatures. The density of defects was determined by photothermal deflection and photoconductivity spectroscopy. The expression of the equilibrium density of defects is obtained starting from the canonical partition function assuming two independent systems of Si‐Si and Si‐C dangling bonds. A weak‐bond defect formation reaction is assumed in the analysis. Linear approximations of the equilibrium temperature and the valence band exponential decay (Urbach’s tail) are used for the numerical calculations. The trend of the experimental data are well represented by the theoretical expression. The model, however, overestimates the density of defects in samples deposite...

In this study, a TiO2 (anatase) nanopowder suspension was processed by high velocity suspension flame spraying (HVSFS). The resulting coatings were characterized and compared to conventional HVOF and atmospheric plasma sprayed layers. It is shown that the HVSFS operating parameters can be adjusted to achieve dense titania with a near nanostructure and homogeneous distribution of anatase and rutile phases. These coatings have lower pore interconnectivity and higher wear resistance than the APS and HVOF layers. Alternatively, large unmelted agglomerates of anatase nanoparticles can be embedded in the coating, increasing the porosity and anatase content for enhanced photocatalytic efficiency.