In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

ObjectiveThere is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.Methods and analysisThis protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE's risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.DisseminationThis systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.PROSPERO registration numberCRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104)

POLARIX: a pathfinder mission of X-ray polarimetry

Since the birth of X-ray astronomy, spectral, spatial and timing observation improved dramatically, procuring a wealth of information on the majority of the classes of the celestial sources. Polarimetry, instead, remained basically unprobed. X-ray polarimetry promises to provide additional information procuring two new observable quantities, the degree and the angle of polarization. POLARIX is a mission dedicated to X-ray polarimetry. It exploits the polarimetric response of a Gas Pixel Detector, combined with position sensitivity, that, at the focus of a telescope, results in a huge increase of sensitivity. Three Gas Pixel Detectors are coupled with three X-ray optics which are the heritage of JET-X mission. POLARIX will measure time resolved X-ray polarization with an angular resolution of about 20 arcsec in a field of view of 15 arcmin $\times$ 15 arcmin and with an energy resolution of 20 % at 6 keV. The Minimum Detectable Polarization is 12 % for a source having a flux of 1 mCrab and 10^5 s of observing time. The satellite will be placed in an equatorial orbit of 505 km of altitude by a Vega launcher.The telemetry down-link station will be Malindi. The pointing of POLARIX satellite will be gyroless and it will perform a double pointing during the earth occultation of one source, so maximizing the scientific return. POLARIX data are for 75 % open to the community while 25 % + SVP (Science Verification Phase, 1 month of operation) is dedicated to a core program activity open to the contribution of associated scientists. The planned duration of the mission is one year plus three months of commissioning and SVP, suitable to perform most of the basic science within the reach of this instrument.Comment: 42 pages, 28 figure

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

LINEE GUIDA PER LA VALUTAZIONE MEDICO- LEGALE DEL DANNO ALLA PERSONA IN AMBITO CIVILISTICO

Le Linee Guida per la valutazione medico-legale del danno alla persona in ambito civilistico sono state strutturate come strumento di suggerimento prioritariamente metodologico improntato ad aggiornate conoscenze per poter pervenire ad una stima ragionata del danno alla persona, inteso quale menomata efficienza psico-fisica comprensiva degli aspetti dinamico-relazionali comuni a tutti. Il testo si compone di una parte Generale, in cui sono affrontati i temi metodologici, e di una parte Sistemica, in cui sono prospettate le valutazioni del danno per singole funzioni

Valutazione medico-legale del danno biologico nella persona anziana. I risultati della consensus conference multidisciplinare

Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields

In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

Systematic review and meta-analysis protocol for in vivo studies describing combination treatments for Gram-negative MDR bacteri

Disorders of early language development in Dravet syndrome

The aim of this study was to investigate language disorders prospectively in patients with Dravet syndrome (DS) during the first years of life in order to identify their features and possibly the underlying mechanisms of the disease. At the Child Neurology Unit of Catholic University in Rome (Italy), thirteen patients with typical findings of DS were enrolled in the study. Full clinical observations, including neurological examination and long-term EEG monitoring, were prospectively and serially performed until a mean of 6 years of age (range: 4 years to 7 years and 8 months). The epileptic history was also collected in each case. In particular, developmental, cognitive, and detailed language assessments were performed with different tests according to the age of the patient.In addition to cognitive decline, characteristic language impairment was also found with a relative preservation of receptive abilities (comprehension) and a strong impairment of productive skills. This defect in sensorimotor verbal processing integration is discussed to highlight the possible mechanisms underlying cognitive decline

VALUTAZIONE MEDICO - LEGALE DEL DANNO BIOLOGICO NELLA PERSONA ANZIANA. I RISULTATI DELLA CONSENSUS CONFERENCE MULTIDISCIPLINARE

L'invecchiamento della popolazione mondiale rappresenta una prova per i sistemi sanitari nazionali e operatori sanitari, compresi gli specialisti in Medicina Legale, che si occupano del danno alla persona in un numero crescente di persone anziane. La valutazione del danno alla persona nelle fasce di età geriatrica è complessa e la scarsità di prove ostacola lo sviluppo di linee guida sull'argomento. L'obiettivo principale della prima Consensus Conference Multidisciplinare sulla valutazione medico-legale del danno biologico nella persona anziana è di accrescere le conoscenze sull'argomento e definire procedure standard in questo campo. La conferenza, organizzata secondo le linee guida emanate dall'Istituto Superiore di Sanità si è tenuta a Bologna l'8 giugno 2019 con il supporto di società scientifiche nazionali, organizzazioni professionali e stakeholder. Il Comitato Tecnico Scientifico ha preparato 16 domande sulle seguenti 4 aree tematiche: - differenze negli esiti delle lesioni traumatiche nelle persone anziane rispetto ai giovani e loro rilevanza nella valutazione del danno biologico; - ricostruzione e valutazione dello stato anteriore; - prassi della visita medico-legale; - valutazione multidimensionale e scale. La segreteria scientifica ha esaminato la letteratura e i documenti pertinenti, ha valutato la loro qualità e riassunto le evidenze. Durante le sessioni pubbliche della conferenza plenaria, 4 coppie di esperti hanno presentato la sintesi della letteratura per ciascuna area tematica. Conclusa l'ultima sessione, una giuria multidisciplinare si è riunita a porte chiuse e ha redatto le dichiarazioni di consenso presentate pubblicamente al termine della conferenza. Sono descritti i metodi e i risultati della Conferenza, il riepilogo delle prove a sostegno delle dichiarazioni della Giuria e le aree che richiedono ulteriori indagini. Le raccomandazioni metodologiche emesse durante la Consensus Conference possono essere utili in diversi contesti di valutazione del danno alla persona, o per altri ambiti della valutazione medico-legale

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields