Prophylactic Activity of Orally Administered FliD-Reactive Monoclonal SIgA Against Campylobacter Infection

This work is licensed under a Creative Commons Attribution 4.0 International License.Campylobacter infection is one of the most common causes of bacterial gastroenteritis worldwide and a major global health threat due to the rapid development of antibiotic resistance. Currently, there are no vaccines approved to prevent campylobacteriosis, and rehydration is the main form of therapy. Secretory immunoglobulin A (SIgA) is the main antibody class found in mucous secretions, including human milk, and serves as the first line of defense for the gastrointestinal epithelium against enteric pathogens. In this study, we describe the prophylactic activity of orally delivered recombinant SIgA generated from two human monoclonal antibodies (CAA1 and CCG4) isolated for their reactivity against the flagellar-capping protein FliD, which is essential for bacteria motility and highly conserved across Campylobacter species associated with severe enteritis. In an immunocompetent weaned mouse model, a single oral administration of FliD-reactive SIgA CAA1 or CCG4 at 2 h before infection significantly enhances Campylobacter clearance at early stages post-infection, reducing the levels of inflammation markers associated with epithelial damage and polymorphonuclear (PMN) cells infiltration in the cecum lamina propria. Our data indicate that the prophylactic activity of CAA1 and CCG4 is not only dependent on the specificity to FliD but also on the use of the SIgA format, as the immunoglobulin G (IgG) versions of the same antibodies did not confer a comparable protective effect. Our work emphasizes the potential of FliD as a target for the development of vaccines and supports the concept that orally administered FliD-reactive SIgA can be developed to prevent or mitigate the severity of Campylobacter infections as well as the development of post-infection syndromes.Bill & Melinda Gates foundation (grant: OPP1170883

Comparing the effects of augmented virtual reality treadmill training versus conventional treadmill training in patients with stage II-III Parkinson’s disease: the VIRTREAD-PD randomized controlled trial protocol

BackgroundIntensive treadmill training (TT) has been documented to improve gait parameters and functional independence in Parkinson’s Disease (PD), but the optimal intervention protocol and the criteria for tailoring the intervention to patients’ performances are lacking. TT may be integrated with augmented virtual reality (AVR), however, evidence of the effectiveness of this combined treatment is still limited. Moreover, prognostic biomarkers of rehabilitation, potentially useful to customize the treatment, are currently missing. The primary aim of this study is to compare the effects on gait performances of TT + AVR versus TT alone in II-III stage PD patients with gait disturbance. Secondary aims are to assess the effects on balance, gait parameters and other motor and non-motor symptoms, and patient’s satisfaction and adherence to the treatment. As an exploratory aim, the study attempts to identify biomarkers of neuroplasticity detecting changes in Neurofilament Light Chain concentration T0-T1 and to identify prognostic biomarkers associated to blood-derived Extracellular Vesicles.MethodsSingle-center, randomized controlled single-blind trial comparing TT + AVR vs. TT in II-III stage PD patients with gait disturbances. Assessment will be performed at baseline (T0), end of training (T1), 3 (T2) and 6 months (T3, phone interview) from T1. The primary outcome is difference in gait performance assessed with the Tinetti Performance-Oriented Mobility Assessment gait scale at T1. Secondary outcomes are differences in gait performance at T2, in balance and spatial–temporal gait parameters at T1 and T2, patients’ satisfaction and adherence. Changes in falls, functional mobility, functional autonomy, cognition, mood, and quality of life will be also assessed at different timepoints. The G*Power software was used to estimate a sample size of 20 subjects per group (power 0.95, α < 0.05), raised to 24 per group to compensate for potential drop-outs. Both interventions will be customized and progressive, based on the participant’s performance, according to a predefined protocol.ConclusionThis study will provide data on the possible superiority of AVR-associated TT over conventional TT in improving gait and other motor and non-motor symptoms in persons with PD and gait disturbances. Results of the exploratory analysis could add information in the field of biomarker research in PD rehabilitation

Fenomeno & Fondamento. Ricerca dell’Assoluto. Studi in onore di Antonio Margaritti

A celebrare il valore umano e intellettuale di Antonio Margaritti è stato convocato da Samuele Pinna e Davide Riserbato, un “nugolo di testimoni” qualificati (se vogliamo adottare la bella immagine di Ebrei 12,1): cardinali e vescovi, teologi e filosofi noti e apprezzati, ex-alunni riconoscenti si sono impegnati a dimostrare, attraverso i loro saggi, che «le maniere semplici» di «un uomo che valeva molto», non sono state «prese per indizio di poco valore». E l’hanno fatto attraverso un arcobaleno di generi letterari. Infatti, dai ricordi personali (…), si procede all’interno dell’orizzonte delle analisi filosofiche e fenomenologiche, si percorre l’ambito teologico fondamentale e sistematico, si compiono incursioni suggestive anche nell’esegesi salmica, si offrono indagini storico-critiche nel pensiero medievale, ma non si ignora neppure la teologia pastoral

Ubi fides ibi libertas. Studi in onore di Giacomo Biffi

Nella sua duplice natura di florilegio di ricordi e di sontuosa teoria di studi sul pensiero e il magistero di Giacomo Biffi, questa raccolta di scritti in suo onore, a un anno dalla scomparsa, si attesta quale evento editoriale assolutamente unico nel suo genere. Doveroso omaggio a una delle figure in assoluto più autorevoli e vivaci del pensiero cristiano e della cultura di ogni tempo, la presente opera costituisce il portale d’accesso per chiunque desideri introdursi nella cattedrale della sua originalissima riflessione. Dall’interno del volume: «Ricordo con gratitudine l’intensa opera pastorale profusa dapprima quale zelante presbitero e vescovo ausiliare di Milano, poi come guida sollecita e saggia» (Papa Francesco). «Pastore esemplare della Chiesa di Dio, (...) Biffi era una personalità, tutto d’un pezzo, uomo di un coraggio straordinario, senza paura di popolarità o impopolarità, orientato solo dalla luce della verità, che in Gesù Cristo ci appare in persona» (Benedetto XVI

Cose nuove e cose antiche

Il presente volume raccoglie alcuni testi di Giacomo Biffi risalenti agli anni del suo ministero sacerdotale milanese (1960-1975). In queste pagine si ritroveranno la stessa forza, la passione e l’umorismo che costituiscono il “marchio di fabbrica” dell’intera produzione del Cardinale. Vi si troveranno parole nuove, giovani e fresche, proprio perché antica è la loro sorgente. Si potrà apprezzare la pastorale chiara e concreta del parroco Biffi, cogliere i fermenti e le speranze dei primi anni del postconcilio, respirare le incertezze e il disorientamento che la società e la Chiesa negli anni della “contestazione” andava sperimentando. Furono gli anni del “miracolo economico”, della “cultura del lavoro”, ma anche anni di crisi e di eventi funesti, di «subbuglio ideologico, morale, ecclesiastico e sociale» (Memorie e digressioni di un italiano cardinale). Mensilmente cadenzata e liturgicamente ritmata, nel suo percorrere diverse volte l’intero ciclo annuale delle stagioni, con le sue rassicuranti monotonie ma anche con le sue sorprendenti e spesso disorientanti novità, questa lettura si configura come una retrospettiva che – per usare le parole dello stesso Giacomo Biffi – «ci dà il senso della continuità della Chiesa (…) al di sopra del mutare degli uomini e delle circostanze. Al di là di tutto ciò che cambia, “Cristo è lo stesso – come sta scritto – ieri e oggi e nei secoli”» (dall’interno del volume

Filastrocche e canarini. Divagazioni letterarie di Giacomo Biffi

A novant\u2019anni dalla nascita di Giacomo Biffi (1928-2015), il volume raccoglie una serie di conversazioni con voci prestigiose della cultura contemporanea che rileggono le passioni letterarie del Cardinale. \uab[\u2026] alle mie Avventure, specchio luminoso delle esigenze pi\uf9 profonde dell\u2019umanit\ue0, si affiancano gli Inni di sant\u2019Ambrogio, espressione pi\uf9 alta di una fede che diviene canto del Mistero, e ancora: Dante con la sua opera divina e immortale, la genuina schiettezza di Giovannino Guareschi, Riccardo Bacchelli con la sua umanissima pietas, la paradossale arguzia di Gilbert Keith Chesterton e l\u2019atmosfera hobbit della Terra di Mezzo di John Ronald Reuel Tolkien, per arrivare infine alle singolari e drammatiche profezie di Vladimir Sergeevi\u10d Solov\u2019\uebv. E non finisce qui: c\u2019\ue8 anche una gustosa conversazione con Giacomo Poretti sul proverbiale umorismo del Cardinale\ubb (dalla Presentazione di Pinocchio

Tutto liscio\u2026 come loglio? Ricapitolazione del disegno unitario

Tutto liscio\u2026 come loglio? \u2013 il titolo allude alla parabola evangelica del grano e della zizzania (il \u201cloglio\u201d, appunto), oggetto della meditazione di Giacomo Biffi che abbiamo posto come Introduzione all\u2019intero volume \u2013 \ue8 una domanda, forse un po\u2019 retorica, che vuole suggerire che quando si coltiva il male, il loglio, nulla pu\uf2 filare via liscio come\u2026 l\u2019oli

Coumarin as attractive casein kinase 2(CK2) inhibitor scaffold: an integrated approach to elucidate the putative binding motif and explain structure-activity relationship.

Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure-activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model

Physical capacity and energy expenditure of cavers

Caves are an extreme environment for humans because of the high humidity, mud, darkness, and slippery conditions. Explorations can last many hours or even days, and require extensive climbing and ropework. Very little is known about the physical capacity of cavers and their energy expenditure (EE) during caving. The physical capacity of 17 (7 females) expert cavers (age 43.9 ± 7.3 years) was assessed during an incremental cycle-ergometer test (IET) with gas exchange analysis. Moreover, a wearable metabolic band (Armband Fit Core) was used to estimate their EE during caving. In terms of physical capacity, the IET showed that cavers had a maximum oxygen uptake (VO2max) of 2,248.7 ± 657.8 ml·min-1 (i.e., 32.4 ± 6.4 ml·kg-1·min-1), while anaerobic threshold (AT) occurred on average at 74.5% of VO2max. Results from caving sessions provided an average time spent in cave of 9.4 ± 1.2 h while the average EE was 268.8 ± 54.8 kcal·h-1, which corresponded to about 40% of VO2max measured during IET. A mean distance of 10.6 ± 2.2 km was covered by subjects. Data from the present investigation provide evidence that cavers have a level of aerobic physical capacity only slightly higher than that of sedentary people, thereby suggesting that a high aerobic fitness is not needed by cavers. Moreover, during caving the EE was on average well below the level of AT. However, in absolute terms, the total EE was elevated (i.e., 2,672.3 ± 576 kcal in total) due to the long time spent in caving. These facts should be taken into account when preparing training as well as diet programs for these athletes