Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis

Muscle dysfunction is a common feature of severe sepsis and multi-organ failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP-3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit ROS production. Using a murine model, we examined metabolic, cardiovascular and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3(-/-) mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Mitochondrial membrane potential was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP-3 protein abundance at 24 hours, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3(-/-) mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and phosphorylation pathway. However, UCP-3 does not play an important functional role, despite its upregulation

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

The chromosomal passenger complex (CPC)-composed of Aurora B kinase, Borealin, Survivin and INCENP-surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes $\textit{in vitro}$. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a 'relay' mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.This work was supported by Cancer Research UK grant no. C12296/A12541 to P.P.D., who is also the recipient of the Maplethorpe Fellowship from Murray Edwards College, Cambridge, UK. I.M. and J.M.E. were supported by Biotechnology and Biological Research Council grant no. BB/J018236/1. A.A.J. is supported by Wellcome Trust Career Development grant no. 095822 and European Commission Career Integration grant no. 334291

Isolation and characterization of buccal fat pad and dental pulp mscs from the same donor

Mesenchymal stem cells (MSCs) can be harvested from different sites in the oral cavity, representing a reservoir of cells useful for regenerative purposes. As direct comparisons between at least two types of MSCs deriving from the same patient are surprisingly rare in scientific literature, we isolated and investigated the osteoinductive potential of dental pulp stem cells (DPSCs) and buccal fat pad stem cells (BFPSCs). MSCs were isolated from the third molar dental pulp and buccal fat pads of 12 patients. The number of viable cells was quantified through manual count. Proliferation and osteodifferentiation assays, flow cytometry analysis of cell phenotypes, and osteocalcin release in vitro were performed. The isolation of BFPSCs and DPSCs was successful in 7 out of 12 (58%) and 3 out of 12 (25%) of retrieved samples, respectively. The yield of cells expressing typical stem cell markers and the level of proliferation were higher in BFPSCs than in DPSCs. Both BFP-SCs and DPSCs differentiated into osteoblast-like cells and were able to release a mineralized matrix. The release of osteocalcin, albeit greater for BFPSCs, did not show any significant difference between BFPSCs and DPSCs. The yield of MSCs depends on their site of origin as well as on the protocol adopted for their isolation. Our data show that BFP is a valuable source for the derivation of MSCs that can be used for regenerative treatments

Comorbidities in rheumatoid arthritis: analysis of hospital discharge records

Objective: Arthritis is often associated with comorbidities. For many of them, such as hypertension, cardiovascular disease, chronic pulmonary disease, and upper gastrointestinal disease, arthritis and its treatment may also represent a risk factor. This study is concerned with an evaluation of the frequency of comorbidities in a cohort of patients with rheumatoid arthritis (RA). Methods: The discharge diagnoses of patients with RA during the period 1 January 1997 to 31 December 2000 were retrieved from the database of the Department of Internal Medicine of the University of Genova, Italy. The diagnosis of RA was made if the patient's discharge record contained the code 714 of the International Classification of Diseases, IX revision, as first 3 numbers. The other diagnoses were also recorded along with demographic data, type and duration of hospital stay, and performed procedures. Results: During the study period, 427 patients with RA were admitted to the hospital for a total number of 761 admissions, which represented 2.2% of total admissions. Ninety-one (21.3%) patients did not have comorbidities, whereas 336 (78.6%) had one or more comorbidities. The most frequently observed comorbidities were cardiovascular diseases (34.6%), including hypertension (14.5%) and angina (3.5%), followed by gastrointestinal (24.5%), genito-urinary (18.7%) and respiratory (17%) diseases. There was a male predominance (p=0.004) within patients with comorbidities, who were significantly older (64.2±3.2 years vs. 57.2±4.2 years; p<0.001) and required longer periods of hospital stay (22.7 days vs. 12.5 days; p<0.001). Conclusions: Comorbidities are present in nearly 80% of RA inpatients. Comorbidity is a good predictor of health outcome, health services utilization, and medical costs. Because RA comorbidity can act as confounder, it should be considered in epidemiologic studies and clinical trials

Sviluppo di modelli innovativi per il monitoraggio multiscala degli indicatori di servizi ecosistemici nelle foreste Mediterranee (Progetto MIMOSE).

Gli ecosistemi, attraverso le loro funzioni, forniscono un ampio range di beni e servizi, che risultano fondamentali per il benessere dell’uomo. Questi vengono complessivamente definiti Servizi Ecosistemici (SE). I SE possono essere intesi come un flusso di valori verso la società, quale risultato dello stato e della quantità del capitale naturale disponibile. Il mantenimento degli stocks del capitale naturale può permettere di prevedere i flussi futuri dei SE, assicurando quindi il benessere dell’uomo per le generazioni future. Il progetto FIRB 2012 MIMOSE è finalizzato allo sviluppo di un approccio multiscala innovativo e all’implementazione di strumenti previsionali volti al monitoraggio dei SE in habitat forestali Mediterranei. Un set di indicatori viene considerato per stimare i SE forniti dalle foreste, sviluppando strumenti integrati per il loro monitoraggio multiscala. Le attività di ricerca vertono allo sviluppo di un metodo statistico innovativo per la stima spaziale degli indicatori di SE, sulla base di dati disponibili a diversi livelli di scala spaziale. Sono realizzate mappe wall-to-wall per la fornitura dei SE, derivate da diversi domini spaziali, dal livello di scala locale sino ad aree forestali di grande estensione. I dati sugli indicatori dei SE sono forniti nel contesto di attività di campionamento già stabilite (raccolta dati a livello di aree di saggio e di popolamento), per poi applicare tecniche di spazializzazione per aggregare i dati raccolti su scala locale a livelli di scala più ampia (paesaggio, scala regionale); l’approccio utilizzato viene valutato attraverso l’applicazione di strumenti di monitoraggio in un set di aree test. Si procede quindi alla valutazione dei cambiamenti spazio-temporali nella previsione dei SE, considerando indicatori sensibili alla gestione forestale, ovvero capaci di evidenziare cambiamenti nella previsione di fornitura di beni e servizi ad opera dei sistemi forestali, in relazione a differenti scenari gestionali, con l’obiettivo di fornire indicazioni ai gestori forestali ed alle comunità locali per l’applicazione di pratiche di gestione che possano mantenere o incrementare la fornitura dei SE in un preciso contesto territoriale. Questo progetto permette di realizzare un’attenta analisi dei gaps esistenti negli attuali schemi di inventariazione in relazione alla fornitura dei SE, con l’obiettivo di dare indicazioni utili all’implementazione ed integrazione degli stessi mediante individuazione di nuovi indicatori, nell’ottica di una gestione forestale sostenibile. Le attività di ricerca in corso possono concretamente contribuire all’incorporazione dei SE nei processi decisionali connessi alla gestione dei paesaggi forestali, fornendo un’opportunità per comprendere la congruenza tra i diversi SE negli ambienti forestali

Adaptive forest governance to face land use change impacts in Italy: a review

Il cambiamento dell’uso del suolo è uno dei driver principali della riduzione della resilienza ecosistemica, così come della perdita di biodiversità e approvvigionamento di servizi. Rappresenta una sfida peculiare, specialmente negli ambienti mediterranei, dove i fenomeni di abbandono e ricolonizzazione naturale stanno minacciando in modo sempre più crescente la capacità delle foreste di fornire benefici alle comunità locali. In queste condizioni, il sistema di governance forestale è chiamato a bilanciare gli impatti del cambiamento dell’uso del suolo con l’assicurazione della salute e della stabilità degli ecosistemi forestali, al fine di garantire la sostenibilità a lungo termine degli ambienti, soprattutto di quelli marginali. Questo lavoro si propone di analizzare in modo più approfondito gli impatti del cambiamento dell’uso del suolo sugli ecosistemi forestali negli ambienti montani italiani. In primo luogo, esegue un’analisi bibliografica dei concetti legati al cambiamento dell’uso del suolo e all’approvvigionamento dei servizi ecosistemici, dalla scala globale a quella locale. In seguito, indaga le relazioni fra le potenzialità adattive di gestione e pianificazione forestali e il cambiamento dell’uso del suolo. Infine, vengono proposte alcune strategie future di possibili strumenti di governance adattiva per affrontare i cambiamenti dell’uso del suolo. Questa infatti può migliorare la resilienza degli ecosistemi forestali riducendo il gap nel campo della ricerca tra il contesto nazionale e quello globale, utilizzando strumenti di valutazione e monitoraggio per simulare cambiamenti e disturbi esterni, e adottando strategie e misure politiche coerenti a scala locale.Land use change is one of the most important drivers for the reduction of ecosystem resilience, and the loss ofbiodiversity and services provision. This is a peculiar challenge, especially in Mediterranean mountain environments,where abandonment and forest transition phenomena increasingly threaten the forest capacity to provide benefits for local communities. Under these conditions, forest governance is called to balance the landuse change impacts and the health and stability of forest ecosystems, in order to ensure the long-term sustainabilityof such marginal environments. This paper aims at deeper understanding the impacts of land use change on forest ecosystem on mountain environments in Italy. At first, a downscaled review on the conceptsof land use change and ecosystem services provision is carried out. Then, according to the review results, therelationships between adaptive capacity of forest management and planning, and land use change is deeply described. Finally, future-oriented strategies of adaptive governance to face land use change are proposed. Inthe context of land use change, adaptive governance can improve forest resilience through filling the researchgaps between the national and the global contexts, adopting monitoring and assessment tools to simulate external changes and disturbances, and effectively implement consistent policy measures and strategies at localscale

Pediatric Critical Care Transfusion and Anemia Expertise Initiative

Introduction/Hypothesis: Despite evidence that a lower hemoglobin threshold is safe in hemodynamically stable children, studies have shown that transfusion thresholds in practice are higher, exposing these children to the morbidity and mortality associated with RBC transfusion. Therefore, there is increased need for evidence-based blood management strategies for clinicians caring for critically ill children. Methods: The Pediatric Critical Care Transfusion and Anemia Expertise Initiative has brought together a group of 49 international experts in pediatric transfusion/critical care in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), to conduct a consensus conference series on pediatric critical care blood management. The methodology is modeled after that used in the Pediatric Acute Lung Injury and Consensus Conference and will create consensus statements via a structured process outlining existing data in RBC transfusion. Novel features include engagement with implementation science experts to enable consensus uptake. Results: Two of the three expert meetings have been successfully conducted. Ten topics were identified and include recommendations on indications for RBC transfusion in critically ill children 1) based on hemoglobin triggers in the general population, 2) based on physiological triggers in the general population, 3) traumatic brain injury, 4) congenital heart disease, 5) hematologic/oncologic disease, 6) respiratory failure, 7) shock, 8) bleeding, 9) extracorporeal support, and 10) alternative processing. The systematic review was performed. The short text recommendations were generated, discussed at the second meeting and will undergo voting using the RAND UCLA Appropriateness Method to achieve consensus. Conclusions: The TAXI consensus series is the first consensus series to convene international and multidisciplinary experts to create consensus statements on transfusion practices to improve outcomes and safety for critically ill children at risk for, or who require, RBC transfusions

PROGETTO LIFE11 ENV IT 215 RESILFORMED - RESILIENZA AL CAMBIAMENTO CLIMATICO NELLE FORESTE MEDITERRANEE

Le condizioni climatiche delle regioni mediterranee, caratterizzate da frequenti annate siccitose, contribuiscono all’indebolimento degli ecosistemi forestali. Come risultato le foreste riducono le loro capacità produttive e sono più soggette a fenomeni di degrado secondario. Inoltre i contesti economico-sociali possono acuire il degrado con la diffusione di uno scorretto uso della risorsa (tagli boschivi, pascolamento) e con la diffusione degli incendi boschivi. L’obiettivo generale del progetto è preservare i sistemi forestali in ambiente mediterraneo dai rischi derivanti dai cambiamenti climatici, tramite processi di naturalizzazione, aumento di biodiversità e migliorata reattività, nei processi di recupero, in seguito ad eventi destabilizzanti. Obiettivo specifico è implementare una politica forestale regionale in grado di aumentare la capacità di resilienza delle foreste siciliane, migliorandone l’efficienza ecosistemica e favorendo la salvaguardia della biodiversità. Tra le azioni principali previste dal progetto, che si concluderà alla fine del 2015, si possono citare la classificazione delle categorie forestali siciliane in funzione della sensibilità alla desertificazione, l’indagine diacronica sull’uso e copertura del suolo dei principali paesaggi forestali siciliani, la definizione di prassi selvicolturali specifiche; la realizzazione di 120 ettari di interventi dimostrativi in 6 aree della Sicilia; la realizzazione di 6 piani di indirizzo forestali attraverso processi partecipativi con le popolazioni locali. Nella fase finale del progetto è prevista l’implementazione delle linee strategiche sperimentate con ResilForMed nel Piano Forestale Regionale della Sicilia

A rapid controller of temperature for use in determining Arrhenius profiles in biomembrane systems

To minimize artifacts in temperature-velocity (Arrhenius) profiles due to aging of preparations of biological membranes, a rapid controller of temperature was developed for spectrophotometric or polarographic (O 2 electrode) measurements. The reaction mixture is cooled or heated through contact with Peltier elements. One Pt temperature sensor in the cuvette or electrode holder controls current flow into the Peltier units, and another Pt temperature sensor in the reaction mixture is used to read out the sample temperature on a meter or recorder, and to provide feedback control. The sample temperature can be reproducibly set to within 0.1°C, with a noise level of 0.04°C or less; a change of 4°C takes 1 min.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44794/1/10863_2004_Article_BF00744744.pd