Relationship between Pre-Implant Interleukin-6 Levels, Inflammatory Response, and Early Outcome in Patients Supported by Left Ventricular Assist Device: A Prospective Study

Purpose: The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among preimplant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients. Methods: In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA $11 was considered as main adverse outcome. Length of ICU-stay, 1 weektSOFA score, hospitalisation and 3-month survival were considered additional end-points. Results: During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score$11. Pre-implant level of IL-6 $ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group. Conclusions: LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome

The Italian Implementation of the EU Directives on Procedural Safeguards for Accused Persons in Criminal Proceedings

Questo saggio è stato sviluppato nel corso di un progetto di ricerca di 30 mesi finanziato dalla Commissione europea - CrossJustice (https://site.unibo.it/cross-justice/en), condotto sotto la supervisione dell'Università di Bologna. L'obiettivo del progetto era verificare il livello di attuazione delle sei direttive sui diritti dell'imputato adottate dal 2009 nell'ambito del Programma di Stoccolma. La ricerca ha esaminato criticamente i diritti dell'imputato riconosciuti e tutelati dalla Direttiva 2010/64/UE del 20 ottobre 2010 sul diritto all'interpretazione e alla traduzione; dalla Direttiva 2012/13/UE del 22 maggio 2012 sul diritto all'informazione; la Direttiva 2013/48/UE sul diritto di accesso a un difensore e di informazione di terzi; la Direttiva 2016/343/UE del 9 marzo 2016 sulla presunzione di innocenza e il diritto di presenziare al processo; la Direttiva 2016/800/UE sulle garanzie procedurali per gli imputati minorenni; la Direttiva 2016/1919/UE del 26 ottobre 2016 sul patrocinio a spese dello Stato. I ricercatori coinvolti hanno combinato due diverse metodologie, esaminando la questione sia da una prospettiva tradizionale, condotta da studiosi specializzati in diritto dell'UE e diritto processuale penale nazionale, sia da una nuova analisi computazionale. Nell'ambito di quest'ultimo approccio, la ricerca ha sviluppato una piattaforma di intelligenza artificiale semi-automatizzata, per evidenziare meglio le lacune scoperte dei testi normativi e migliorare l'analisi comparativa tra i sistemi giuridici (https://www.crossjustice.eu/en/index.html#crossjustice-platform)   Il presente contributo si concentra – adottando un metodo tradizionale - sul modo in cui il legislatore italiano ha recepito e attuato le suddette direttive, sia con riferimento alle disposizioni normative sia nell'interpretazione giudiziaria dei vertici del sistema. Infatti, mentre l'acquis dell'UE stabilisce standard minimi comuni in materia di diritti processuali penali, la necessità di promuoverne un'applicazione efficace e coerente rimane particolarmente pressante a causa della forte frammentazione della legislazione nazionale e della relativa giurisprudenza. In termini generali, il quadro che emerge mostra alcuni punti di forza del sistema italiano, con particolare riferimento al diritto al difensore, al diritto all'informazione e alla disclosure (e, in misura meno uniforme, alle regole di esclusione probatoria quando si tratti di tutelare le violazioni delle garanzie difensive). Non mancano tuttavia alcune criticità, spesso legate alla prassi (ad esempio, la necessaria formazione che i difensori degli imputati vulnerabili dovrebbero ricevere, il patrocinio a spese dello Stato, la qualità e l'efficacia del diritto all'interprete e la tradizione degli atti). La presente analisi del sistema italiano, insieme a quella sviluppata per gli altri 10 Stati Membri dell’UE coinvolti nel progetto (Bulgaria, Croazia, Francia, Germania, Paesi Bassi, Polonia, Portogallo, Romania, Spagna, Svezia) ed ai risultati dell’analisi semantica dei testi normativi, fondata su tecniche di Intelligenza Artificiale, ha consentito di sviluppare una ricerca innovativa nei metodi e nei contenuti, che, oltre alla piattaforma Crossjustice, ha trovato recente pubblicazione anche in un volume edito da Brill (Giuseppe Contissa, Giulia Lasagni, Michele Caianiello, Giovanni Sartor (eds.), Effective Protection of the Rights of the Accused in the EU Directives. A Computable Approach to Criminal Procedure Law, 2022)

A Plant Gene Encoding One-Heme and Two-Heme Hemoglobins With Extreme Reactivities Toward Diatomic Gases and Nitrite

In plants, symbiotic hemoglobins act as carriers and buffers of O2 in nodules, whereas nonsymbiotic hemoglobins or phytoglobins (Glbs) are ubiquitous in tissues and may perform multiple, but still poorly defined, functions related to O2 and/or nitric oxide (NO). Here, we have identified a Glb gene of the model legume Medicago truncatula with unique properties. The gene, designated MtGlb1-2, generates four alternative splice forms encoding Glbs with one or two heme domains and 215–351 amino acid residues. This is more than double the size of any hemoglobin from plants or other organisms described so far. A combination of molecular, cellular, biochemical, and biophysical methods was used to characterize these novel proteins. RNA-sequencing showed that the four splice variants are expressed in plant tissues. MtGlb1-2 is transcriptionally activated by hypoxia and its expression is further enhanced by an NO source. The gene is preferentially expressed in the meristems and vascular bundles of roots and nodules. Two of the proteins, bearing one or two hemes, were characterized using mutants in the distal histidines of the hemes. The Glbs are extremely reactive toward the physiological ligands O2, NO, and nitrite. They show very high O2 affinities, NO dioxygenase activity (in the presence of O2), and nitrite reductase (NiR) activity (in the absence of O2) compared with the hemoglobins from vertebrates and other plants. We propose that these Glbs act as either NO scavengers or NO producers depending on the O2 tension in the plant tissue, being involved in the fast and fine tuning of NO concentration in the cytosol in response to sudden changes in O2 availability

Commentary

Commentary of decisions of the International Criminal Court on the change of location of proceedings

The United Nations 'quasi-prosecutorial' investigative mechanisms: assessing a new institutional model in the international criminal justice landscape

This work aims to provide a theoretical examination of three recently created bodies of the United Nations mandated to investigate the alleged international crimes committed in Syria (IIIM), Iraq (UNITAD) and Myanmar (IIMM). Established as a compromise solution in the paralysis of international criminal jurisdictions, these essentially overlapping entities have been depicted as a ‘new generation’ of UN investigative mechanisms. While non-judicial in nature, they depart indeed from traditional commissions of inquiry in several respects due to their increased criminal or ‘quasi-prosecutorial’ character. After clarifying their legal basis and different mandating authorities, a comparative institutional analysis is thus carried out in order to ascertain whether these ‘mechanisms’ can be said to effectively represent a new institutional model. Through an in-depth assessment of their mandates, the thesis is also intended to outline both the strengths and the criticalities of these organs. Given their aim to facilitate criminal proceedings by sharing information and case files, it is suggested that more attention shall be paid to the position of the person under investigation. To this end, some proposals are made in order to enhance the mechanisms’ frameworks, especially from the angle of procedural safeguards. As a third aspect, the cooperation with judicial authorities is explored, in order to shed light on the actors involved, the relevant legal instruments and the possible obstacles, in particular from a human rights perspective. Ultimately, drawing from the detected issues, the thesis seeks to identify some lessons learned which could be taken into account in case of creation of new ad hoc investigative mechanisms or of a permanent institution of this kind

Longitudinal Nutritional Intakes in Italian Pregnant Women in Comparison with National Nutritional Guidelines

Background: Nutritional quality during pregnancy is crucial for mother and child health and their short/long-term outcomes. The aim of this study is to evaluate the adherence to nutritional recommendations in Italy during the three pregnancy trimesters in Normal Weight (NW) and Over Weight (OW) women. Methods: Data from a multicenter randomized controlled trial included 176 women (NW = 133; OW = 43) with healthy singleton pregnancies enrolled within 13 + 6 weeks of gestation. Dietary intake was assessed every trimester by a Food Frequency Questionnaire. Results: OW and NW had similar gestational weight gain. However, as Institute of Medicine (IOM) recommend lower gestational weight gain (GWG) for OW, they exceeded the suggested range. In both groups, caloric intake during the three trimesters never met recommendations. Protein intake in first and second trimester was higher than recommendations, as was sugars percentage. Dietary fiber intake was lower in OW. Polyunsaturated fatty acids, calcium, iron and folic acid requirements were never satisfied, while sodium intake exceeded recommendations. Conclusions: NW and OW women in Italy do not adhere to nutritional recommendations during pregnancy, with lower caloric intake, protein and sugars excess and inadequacies in micronutrients intake. Pregnant women in Italy should be provided with an adequate counseling and educational intervention as well as supplementation when indicated

Balance and walking involvement in Facioscapulohumeral Muscular Dystrophy (FSHD): a pilot study on the effects of custom lower limb orthoses

BACKGROUND: Autosomal dominant facioscapulohumeral dystrophy (FSHD), the third most common muscular dystrophy, is characterised by asymmetric and highly variable muscle weakness. In FSHD patients, the coupling of the ankle muscles impairment with the knee, hip and abdominal muscles impairment, causes complex alterations of balance and walking with deterioration of quality of life (QoL). AIM: The aim of this pilot study is to evaluate the effects of custom orthoses (foot orthosis-FO and ankle foot orthosis-AFO) on balance, walking and QoL of FSHD patients through a multidimensional approach. DESIGN: Pilot study. SETTING: Outpatient Rehabilitation Department of Don Gnocchi Foundation. POPULATION: Fifteen patients with facioscapulohumeral muscular dystrophy were studied. METHODS: On 15 FSHD patients clinical evaluation (Manual Muscle Test-MMT, Clinical Severity Score), performance tests (10 meter Walking test-10mWT and 2 minute Walking Test-2minWT), instrumental assessment (stabilometric evaluation), disability (Rivermead Mobility Index- RMI, Berg Balance Scale-BBS) and patient-oriented (Medical Outcome Study 36-item Short Form-SF-36, North American Spine Society-NASS and Visual Analogue Scale-VAS) measures were performed. Patients were evaluated first, wearing their shoes and then wearing their shoes plus orthoses. This evaluation was performed 1 month after wearing the orthoses. RESULTS: The shoes plus orthoses evaluation, performed after one month in which the patients daily wore the custom lower limb orthoses, showed a significant improvement of walking performance (10-mWT p<0.01), balance (Romberg Index p<0.05; Medio-Lateral Velocity p<0.05) and QoL (PCS p<0.01). CONCLUSION: This pilot study shows that in FSHD patients\u2019 custom lower limb orthoses (foot-orthoses and ankle-foot-orthoses); evaluated by using a multidimensional approach, improve walking, balance and QoL. CLINICAL REHABILITATION IMPACT: These preliminary results suggest that custom lower limb orthoses could reduce the risk of falling with a positive effect on our patients\u2019 safety. Our results should encourage the scientific community to do efficacy study on this hot topic