Publications by authors named "Elena Bravo"

50 Publications

Biobanking in the COVID-19 Era and Beyond: Part 1. How Early Experiences Can Translate into Actionable Wisdom.

Biopreserv Biobank 2020 Dec 6;18(6):533-546. Epub 2020 Nov 6.

BioConsulting, Cork, Ireland.

The era of COVID-19 has brought about a number of novel challenges for the global biobanking community. To better position the biobanking community to cope with current and future challenges, the International Society for Biological and Environmental Repositories (ISBER) COVID-19 Response Task Force was convened to identify needs and gaps in biobanking tools (existing resources that support good practice), for example, standards, best practices, business, etc. and to make recommendations to benefit the community. Toward these goals, the Task Force assembled a set of questions to explore individual biobanks' experiences, with emphasis on identification of key challenges and approaches, including tools employed. A survey was designed with the use of these questions and administered by ISBER. This article presents a summary of the aggregated data obtained from the survey responses, illustrating some of the major issues encountered and identifying which tools the survey respondents found most useful. In particular, this article focuses on the challenges identified during the early months of the COVID-19 era. Recommendations are provided to support biobank emergency preparedness for the future, address lessons learned, and propose solutions to bridge identified gaps. The analysis and the complete survey dataset will also inform the larger Task Force goal to develop specific tool recommendations.
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http://dx.doi.org/10.1089/bio.2020.0082DOI Listing
December 2020

Two phase I/II clinical trials for the treatment of urinary incontinence with autologous mesenchymal stem cells.

Stem Cells Transl Med 2020 12 31;9(12):1500-1508. Epub 2020 Aug 31.

New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Madrid, Spain.

We evaluated the safety and feasibility of adipose-derived mesenchymal stem cells to treat endoscopically urinary incontinence after radical prostatectomy in men or female stress urinary. We designed two prospective, nonrandomized phase I-IIa clinical trials of urinary incontinence involving 9 men (8 treated) and 10 women to test the feasibility and safety of autologous mesenchymal stem cells for this use. Cells were obtained from liposuction containing 150 to 200 g of fat performed on every patient. After 4 to 6 weeks and under sedation, endoscopic intraurethral injection of the cells was performed. On each visit (baseline, 1, 3, 6, and 12 months), clinical parameters were measured, and blood samples, urine culture, and uroflowmetry were performed. Every patient underwent an urethrocystoscopy and urodynamic studies on the first and last visit. Data from pad test, quality-of-life and incontinence questionnaires, and pads used per day were collected at every visit. Statistical analysis was done by Wilcoxon signed-rank test. No adverse effects were observed. Three men (37.5%) and five women (50%) showed an objective improvement of >50% (P < .05) and a subjective improvement of 70% to 80% from baseline. In conclusion, intraurethral application of stem cells derived from adipose tissue is a safe and feasible procedure to treat urinary incontinence after radical prostatectomy or in female stress urinary incontinence. A statistically significant difference was obtained for pad-test improvement in 3/8 men and 5/10 women. Our results encourage studies to confirm safety and to analyze efficacy.
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http://dx.doi.org/10.1002/sctm.19-0431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695632PMC
December 2020

Musculo-skeletal problems of the hand in haemophilia.

EFORT Open Rev 2020 Jun 1;5(6):328-333. Epub 2020 Jun 1.

Haemophilia Orthopedic Unit, Orthopedic Surgery Department, Hospital Universitario La Paz, Madrid, Spain.

Musculo-skeletal complications of the hand in the haemophilia patient are rare, and they include synovitis, arthropathy, pseudotumours, carpal tunnel syndrome and vascular aneurysms and pseudoaneurysms.The best way to prevent the aforementioned musculo-skeletal complications is early continuous haematological primary prophylaxis (intravenous infusion of the deficient coagulation factor, ideally from cradle to death).There is a wide range of procedures that a hand surgeon treating these patients should be able to manage, including synovectomy, prosthetic replacement of small joints, removal or curettage of pseudotumours, release of carpal tunnel and, occasionally, vascular reconstruction of aneurysms.The treatment of these patients should be made at an institution with close collaboration between haematologists and hand surgeons (all surgical procedures must always be performed under cover of the deficient coagulation factor). Cite this article: 2020;5:328-333. DOI: 10.1302/2058-5241.5.190078.
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http://dx.doi.org/10.1302/2058-5241.5.190078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336188PMC
June 2020

Caveolin-1 Endows Order in Cholesterol-Rich Detergent Resistant Membranes.

Biomolecules 2019 07 17;9(7). Epub 2019 Jul 17.

National Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, Italy.

Cholesterol-enriched functional portions of plasma membranes, such as caveolae and rafts, were isolated from lungs of wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mice within detergent resistant membranes (DRMs). To gain insight into their molecular composition we performed proteomic and lipid analysis on WT and Cav-1 KO-DRMs that showed predicted variations of proteomic profiles and negligible differences in lipid composition, while Langmuir monolayer technique and small and wide-angle X-ray scattering (SAXS-WAXS) were here originally introduced to study DRMs biophysical association state. Langmuir analysis of Cav-1 containing DRMs displayed an isotherm with a clear-cut feature, suggesting the coexistence of the liquid-ordered () phase typical of the raft structure, namely "cholesterol-rich phase," with a phase fully missing in Cav-1 KO that we named "caveolin-induced phase." Furthermore, while the sole lipid component of both WT and KO-DRMs showed qualitatively similar isotherm configuration, the reinsertion of recombinant Cav-1 into WT-DRMs lipids restored the WT-DRM pattern. X-ray diffraction results confirmed that Cav-1 causes the formation of a "caveolin-induced phase," as suggested by Langmuir experiments, allowing us to speculate about a possible structural model. These results show that the unique molecular link between Cav-1 and cholesterol can spur functional order in a lipid bilayer strictly derived from biological sources.
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http://dx.doi.org/10.3390/biom9070287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680987PMC
July 2019

[The biological resources and molecule archives organization: turn a need into an opportunity for the Smart Specialization Strategy of the Lazio region.]

Recenti Prog Med 2019 Feb;110(2):68-74

Istituto Superiore di Sanità, Roma.

Smart Specialization Strategy (S3) of Lazio defines smart specialization strategies to bring out the excellence of the territory with prospects of success on the global market. Chemical-pharmaceutical, biomedical and biotechnological field is one of the 7 sectors considered of greatest interest for the S3. Key engine of biotechnology development are biological materials and associated data, stored in biobanks. However, to ensure that the research and product development carried out with that resources gives statistically significant and reproducible results, it is essential that they are collected, manipulated and stored using standardized and traced methods. Implementation of the recent published standard ISO 20387- "Biotechnology-Biobanking-General requirements for biobanking" is bridging biobanks toward to storage and distribution of qualified biological material only. Human biobanks are also an essential part of the assistance and care of the citizen and constitute an unavoidable cost of the regional health system. However, biobanks organization, rationalization of their territorial distribution, completion of the process of recognition and regional accreditation, parallel to the implementation of the offer of remunerated services for biobanking, can turn the cost of the necessary preservation of the samples, into an opportunity of territorial development. The paper describes the necessity, shared by a working group represented by several Lazio biobanks, of including biobank activities in the virtuous circle designed by the S3,concretizing the framework prefigured by the S3 document on infrastructures for research, innovation and technology transfer. To allow inclusion of biobank activities in the virtuous circle, we underline the need to quickly start the process of recognition of the territorial research biobanks, to implement at regional level the process of optimization and rationalization of the management of biological samples, in accordance with the international harmonization standards and with the territorial indications of sustainability.
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http://dx.doi.org/10.1701/3112.31001DOI Listing
February 2019

Improving Provision of Care for Long-term Survivors of Lymphoma.

Clin Lymphoma Myeloma Leuk 2017 Dec 17;17(12):e1-e9. Epub 2017 Aug 17.

Hematology and Cell Therapy Unit, IRCCS-Istituto Tumori "Giovanni Paolo II", Bari, Italy.

The progressive improvement of lymphoma therapies has led to a significant prolongation of patient survival and life expectancy. However, lymphoma survivors are at high risk of experiencing a range of early and late adverse effects associated with the extent of treatment exposure. Among these, second malignancies and cardiopulmonary diseases can be fatal, and neurocognitive dysfunction, endocrinopathy, muscle atrophy, and persistent fatigue can affect patients' quality of life for decades after treatment. Early recognition and reduction of risk factors and proper monitoring and treatment of these complications require well-defined follow-up criteria, close coordination among specialists of different disciplines, and a tailored model of survivorship care. We have summarized the major aspects of therapy-related effects in lymphoma patients, reviewed the current recommendations for follow-up protocols, and described a new hospital-based model of survivorship care provision from a recent multicenter Italian experience.
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http://dx.doi.org/10.1016/j.clml.2017.08.097DOI Listing
December 2017

Business Planning in Biobanking: How to Implement a Tool for Sustainability.

Biopreserv Biobank 2017 Feb 29;15(1):46-56. Epub 2016 Nov 29.

2 Departments of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità , Rome, Italy .

Worldwide, the sustainability of public health systems is challenged by the increasing number and cost of personalized therapies. Quality biological samples stored in biobanks are essential for the provision of appropriate health services and also act as a reservoir for the development of precision medicine and biotechnological innovation. Economic sustainability is a crucial factor in the maintenance of biobanking activities. Traditionally, management of biobanking is performed by health researchers and/or clinicians whose knowledge of economic issues is inadequate. On the other hand, familiarity with financial instruments used by economists is not often accompanied by a consolidated understanding of biobanking features. This article aims to be a guide for the implementation of business plans in biobanking and proposes models for the facilitation of their preparation, thus contributing to recognition of the importance of efficient management of resources of public health services.
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http://dx.doi.org/10.1089/bio.2016.0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327055PMC
February 2017

Mesenchymal stromal cells as multifunctional cellular therapeutics - a potential role for extracellular vesicles.

Transfus Apher Sci 2016 Aug 15;55(1):62-9. Epub 2016 Jul 15.

Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.

Mesenchymal stromal cells (MSCs), multipotent cells present in tissues throughout the body, can reconstitute adipogenic, osteogenic and chondrogenic tissues, but are also of great interest as mediators of immune modulation and suppression. MSCs are able to improve transplant engraftment, treat graft versus host disease and suppress T cell responses and therefore have great potential as therapeutic agents. Their immune modulatory capacity is mediated through both cell-to-cell contact and cytokine secretion, but it is becoming clear that extracellular vesicles (EV) produced by MSC also possess immunomodulatory properties. These vesicles are easy to prepare and store, do not carry nuclear material and cannot form tumours, and therefore also represent a highly desirable therapeutic agent. This review outlines the formation and characterisation of extracellular vesicles, the reported function of MSC-EVs in vitro and in vivo, and addresses some of the emerging issues with nomenclature, EV therapeutic dose and tissue source. The development of GMP-grade production protocols and effective characterisation of MSC extracellular vesicles is essential to their successful use as immune modulating therapeutic agents, and this review outlines the current status of the research in this area.
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http://dx.doi.org/10.1016/j.transci.2016.07.011DOI Listing
August 2016

Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles.

Biopreserv Biobank 2016 Aug 17;14(4):350-2. Epub 2016 Jun 17.

2 Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità , Rome, Italy .

Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The "BRIF (Bioresource Research Impact Factor) and journal editors" subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing.
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http://dx.doi.org/10.1089/bio.2015.0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991644PMC
August 2016

The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression.

Nutrients 2015 Dec 1;7(12):9834-46. Epub 2015 Dec 1.

Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy.

Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties. NAFLD has been shown to be associated with disturbances in plasma and liver CoQ concentrations, but the relationship between these changes and disease development and progression is not yet clear. Dietary supplementation with CoQ has been found to be hepatoprotective and to reduce oxidative stress and inflammation as well as improving mitochondrial dysfunction, suggesting that it may be beneficial in NAFLD. However, studies using animal models or patients with NAFLD have given inconclusive results. Overall, evidence is now emerging to indicate that disturbances in CoQ metabolism are involved in NAFLD development and progression to NASH, and this highlights the need for further studies with human subjects to fully clarify its role.
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http://dx.doi.org/10.3390/nu7125501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690053PMC
December 2015

Developing a guideline to standardize the citation of bioresources in journal articles (CoBRA).

BMC Med 2015 Feb 17;13:33. Epub 2015 Feb 17.

Background: Many biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles.

Methods: As standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors' networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops.

Results: The European Association of Science Editors has adopted BRIF's suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual "reference [BIORESOURCE]" according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their "guidelines under development" section.

Conclusions: Evaluating bioresources' use and impact requires that publications accurately cite such resources. Adopting the standard citation scheme described here will improve the quality of bioresource reporting and will allow their traceability in scientific publications, thus increasing the recognition of bioresources' value and relevance to research. Please see related article: http://dx.doi.org/10.1186/s12916-015-0284-9.
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http://dx.doi.org/10.1186/s12916-015-0266-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331335PMC
February 2015

Development of a pilot project on data sharing among partners of the Italian Hub of Population Biobanks (HIBP): association between lipid profile and socio-demographic variables.

Biopreserv Biobank 2014 Aug 30;12(4):225-33. Epub 2014 Jul 30.

1 Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità , Rome, Italy .

The Italian Hub of Population Biobanks (HIBP) includes both ongoing and completed studies that are heterogeneous in both their purpose and in the specimens collected. The heterogeneity in starting conditions makes sharing study data very difficult because of technical, ethical, and collection rights issues that hamper collaboration and synergy. With the aim of overcoming these difficulties and establishing the "proof-of-concept" that sharing studies is achievable among Italian collections, a data-sharing pilot project has been agreed to by HIBP members. Participants agreed to the general methodology and signed a shared Data Transfer Agreement. The biobanks involved were: EURAC (Micros study), CIG (GEHA project), CNESPS (FINE, MATISS, MONICA, OEC1998, ITR (Italian Twin Register), and IPREA studies, and MOLIBANK (Moli-Sani project). Biobank data were uploaded into a common database using a dedicated informatics infrastructure. Demographic data, and anthropometric and hematochemical parameters were shared for each record. Each biobank uploaded into the common database a dataset with a minimum of 1000 subjects, for a total of 5071 records. After a harmonization process, the final dataset included 3882 records. Subjects were grouped into three main geographic areas of Italy (North, Center, and South) and separate analyses were performed for men and women. The 3882 records were analyzed through multivariate logistic regression analysis. Results were expressed as odds ratios with 95% confidence interval. Results show several geographical differences in the lipidemic pattern, mostly regarding cholesterol-HDL, which represents a strong basis for further, deeper sample-based studies. This HIBP pilot study aimed to prove the feasibility of such collaborations and it provides a methodological prototype for future studies based on the participation in the partnership of well-established quality collections.
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http://dx.doi.org/10.1089/bio.2014.0001DOI Listing
August 2014

The European Research Infrastructures of the ESFRI Roadmap in Biological and Medical Sciences: status and perspectives.

Ann Ist Super Sanita 2014 ;50(2):178-85

Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Rome, Italy.

Introduction: Since 2002, the European Strategy Forum on Research Infrastructures identified the needs for Research Infrastructures (RIs) in Europe in priority fields of scientific research and drafted a strategic document, the ESFRI Roadmap, defining the specific RIs essential to foster European research and economy. The Biological and Medical Sciences RIs (BMS RIs) were developed thanks to the active participation of many institutions in different European member states associated to address the emerging needs in biomedicine and, among these, the Italian National Institute of Health (ISS), in virtue of its role in public health and research, has been specifically involved in the national development and implementation of three RIs: the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI), the European Advanced Translational Research Infrastructure in Medicine (EATRIS) and the European Clinical Research Infrastructures Network (ECRIN).

Aim: This article outlines the design and development of these RIs up to the recent achievement of the ERIC status, their importance in the Horizon 2020 programme and their societal and economic potential impact, with special attention to their development and significance in Italy.

Conclusions: The ISS plays a unique role in fostering a coordinated participation of excellence Italian institutes/facilities to different European biomedical RIs, thus contributing to health innovation, healthcare optimization, and healthcare cost containment.
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http://dx.doi.org/10.4415/ANN_14_02_12DOI Listing
September 2015

Open data sharing in the context of bioresources.

Acta Inform Med 2013 Dec 4;21(4):291-2. Epub 2013 Dec 4.

Istituto Superiore di Sanità, Rome, Italy.

Recently many international initiatives have been developed to improve access to scientific information and to promote open data sharing. In the complex field of bioresources, the BRIF (Bioresource Research Impact Factor) project aims to create suitable methods to recognise and measure the use and impact of biological resources in scientific/academic work, in order to maximize access by researchers to collections of biological materials and attached databases, and to recognize efforts involved in their maintenance. The lack of a proper recognition of scientific contribution is in fact a major obstacle which impedes bioresource sharing. In this context, the BRIF initiative can be considered as a tool to facilitate research resource sharing.
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http://dx.doi.org/10.5455/aim.2013.21.291-292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916190PMC
December 2013

The Italian Hub of Population Biobanks as a potential tool for improving public health stewardship.

Biopreserv Biobank 2013 Jun;11(3):173-5

In Italy, a country that is experiencing the decentralization of health services from central to regional level of government, the Minister of Health is proposing stewardship as a model of governance for the public health system. Stewardship favors efficiency in the policy decision-making process, based on reciprocal trust, and tends to be more ethical. The embryonic proposal to test stewardship in the field of population-based research was advanced during the launching conference Challenges and Opportunities of the Italian Hub of Population Biobanks (HIBP) held in 2012 in Rome. Resources collected by population biobanks (i.e., blood and its derivatives, and/or DNA isolated from any type of biological samples and relative associated data) have, in fact, a recognized scientific value for the investigation of links between genetics, health and life style, and epidemiological outcomes through population biobank-based studies, and are essential to planning effective and qualified interventions for public health. The current economic crisis requires a strong push to rationalize investment in health policies. In particular, population biobank-based studies require financial commitment, often of long duration, for the realization of their goals. Thus, innovative solutions to allow fast integration of scientific knowledge into political health strategy are required. During the conference in Rome, it was proposed to test the stewardship model by its application to the inter-relationship between population biobank-based studies and disease prevention. Stewardship minimizes barriers to innovation and uses information more effectively to better develop new strategies for prevention and/or treatment. In the months following the conference, the proposal was defined more clearly, and the HIBP network became a potential tool for testing and implementing this model in the Italian Public Health prevention system.
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http://dx.doi.org/10.1089/bio.2012.0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696929PMC
June 2013

Review of the Italian current legislation on research biobanking activities on the eve of the participation of national biobanks’ network in the legal consortium BBMRI-ERIC.

Biopreserv Biobank 2013 Apr;11(2):124-8

The ethical-legal framework of research biobanking activities is still scarcely defined in Italy, and this constitutes a major obstacle to exploit the potential benefits of existing bioresource patrimony at the national and international levels. Biobanking and Biomolecular Resources Research Infrastructure (BBMRI), which aims to become a major interface between biological samples and data and top-level biological and medical research, is undertaking the crucial transformation to the ERIC (European Research Infrastructure Consortium) legal entity. In this scenario, there is a need to address the national legal and ethical concerns that are strictly correlated with the use of human biosources in research across European countries participating (and not) in BBMRI. In this perspective, this article aims to review the legal framework applying to research biobanking in Italy, including both "soft" nonbinding instruments and binding regulations. Since ethical and societal aspects impact biobanking research activities, the article discusses both the critical ethical and legal open issues that need to be implemented at the national level.
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http://dx.doi.org/10.1089/bio.2012.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696949PMC
April 2013

Postprandial human triglyceride-rich lipoproteins increase chemoattractant protein secretion in human macrophages.

Cytokine 2013 Jul 15;63(1):18-26. Epub 2013 May 15.

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanitá, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address:

This study tested the hypothesis that postprandial triglyceride-rich lipoproteins (ppTGRL) have inflammatory effects in primary human monocyte-derived macrophages (HMDM). ppTGRL were isolated from normolipidemic human volunteers, and the production of chemokines and of inflammatory prostaglandins and leukotrienes via the arachidonic acid cascade in HMDM was determined, and their effect on monocyte chemotaxis were assessed. In addition, the possible role of extracellular lipases in the inflammatory effects of ppTGRL was evaluated. ppTGRL were found to increase the secretion of chemoattractants, including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α and -1β and IL-8, by HMDM and to have a stimulatory effect on monocyte chemotaxis. HMDM secretion of leukotrienes B4 (LTB4) and lipoxin A (LXA4), which are potent activators of monocyte migration, was also stimulated by ppTGRL. Inclusion of the lipoprotein lipase (LPL) inhibitor orlistat did not alter the effects of ppTGRL on chemokine production, and the expression of mRNA for LPL and other secreted lipases was unaffected by the lipoproteins. These findings support the hypothesis that ppTGRL induce the secretion of chemokines by macrophages which promote monocyte recruitment, and that extracellular lipolysis of the particles is not required for these effects and provide further evidence to indicate that the postprandial lipoproteins contribute to a pro-atherogenic pattern after a fat-rich meal.
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http://dx.doi.org/10.1016/j.cyto.2013.04.025DOI Listing
July 2013

Quantifying the use of bioresources for promoting their sharing in scientific research.

Gigascience 2013 May 1;2(1). Epub 2013 May 1.

Epidémiologie et analyses en santé publique, Faculté de médecine, UMR1027 INSERM-Université de Toulouse III, 37 allées Jules Guesde, Toulouse Cedex 7, F-31073, France.

An increasing portion of biomedical research relies on the use of biobanks and databases. Sharing of such resources is essential for optimizing knowledge production. A major obstacle for sharing bioresources is the lack of recognition for the efforts involved in establishing, maintaining and sharing them, due to, in particular, the absence of adequate tools. Increasing demands on biobanks and databases to improve access should be complemented with efforts of end-users to recognize and acknowledge these resources. An appropriate set of tools must be developed and implemented to measure this impact.To address this issue we propose to measure the use in research of such bioresources as a value of their impact, leading to create an indicator: Bioresource Research Impact Factor (BRIF). Key elements to be assessed are: defining obstacles to sharing samples and data, choosing adequate identifier for bioresources, identifying and weighing parameters to be considered in the metrics, analyzing the role of journal guidelines and policies for resource citing and referencing, assessing policies for resource access and sharing and their influence on bioresource use. This work allows us to propose a framework and foundations for the operational development of BRIF that still requires input from stakeholders within the biomedical community.
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http://dx.doi.org/10.1186/2047-217X-2-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655103PMC
May 2013

Role of macrophage activation in the lipid metabolism of postprandial triacylglycerol-rich lipoproteins.

Exp Biol Med (Maywood) 2013 Jan;238(1):98-110

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

The potential link between the inflammatory effects of postprandial lipemia and the induction of macrophage foam cell formation by triacylglycerol-rich lipoproteins (TGRL) was studied using postprandial triacylglycerol-rich lipoproteins (ppTGRL) derived from human volunteers and primary human monocyte-derived macrophages (HMDM). Subjects were fed a test meal high in dairy fat, followed three hours later by isolation of serum ppTGRL. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes were induced in HMDM by treatment with lipopolysaccharide (LPS) or dexamethasone (DEX), respectively. ppTGRL caused a dose-dependent increase in both triacylglycerol (TG) and cholesterol (CH) accumulation in the cells. TG accumulation was unaffected by LPS or DEX treatment, but LPS as compared with DEX-treated HMDM were found to accumulate more CH, and this effect was greater than that induced by ppTGRL in untreated cells. LPS-treatment had no effect on lipid uptake from ppTGRL (via the LDLr, scavenger receptors or SR-B1) or on CH efflux, but the CH synthesis inhibitor mevinolin abolished the difference between CH accumulation in LPS-and DEX-treated cells, suggesting that CH synthesis is enhanced in the inflammatory state. Phospholipid (PL) synthesis was increased in inflammatory M1 as compared with anti-inflammatory M2 HMDM. Moreover, TG synthesis was decreased by ppTGRL in DEX-treated as compared with untreated cells. We conclude, therefore, inflammation causes a greater increase in the accumulation of neutral lipids than ppTGRL in macrophages, and that this effect is related to modulation of PL metabolism and possibly also CH synthesis. Thus, the inflammatory phenotype of macrophages influences their lipid metabolism, and is, therefore, likely to modulate the induction of macrophage lipid accumulation by lipoproteins associated with foam cell formation.
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http://dx.doi.org/10.1258/ebm.2012.012091DOI Listing
January 2013

Where on earth to publish? A sample survey comparing traditional and open access publishing in the oncological field.

J Exp Clin Cancer Res 2013 Jan 22;32. Epub 2013 Jan 22.

Publishing Unit, Istituto Superiore di Sanità, Rome, Italy.

Background: The paper intends to help scientific authors to make the best choice of journals in which to publish, by describing and comparing journal features in the area of oncology. For this purpose, the authors identified impact factor (IF) ranking, cost options and copyright conditions offered to authors wishing to publish in full open access (OA), subscription-based or hybrid journals.

Methods: Data referring to articles published in 2010 by three Italian research institutions (National Institute of Health - Rome (ISS), Regina Elena National Cancer Institute - Rome (IRE), National Cancer Institute - Milan (INT) in journals (78) managed according to different business models, all listed in the Journal Citation Reports, subject category Oncology, were collected and analysed. The journals surveyed were ranked according to IF, position in quartiles, publication charges, usage rights in published articles, self-archiving conditions in OAI-compliant repositories digital archives.

Results: Almost half (34) the journals surveyed were included in the first quartile, thus revealing authors' preference for journals with a high IF. The prevalent journal business model was the hybrid formula (based on subscriptions but also offering a paid OA option) with 51 journals, followed by subscription-based only journals accounting for 22, while just 5 full OA journals were identified. In general, no relationship was found between IF and article publication charges, in terms of correspondence between more expensive fees and higher IF.

Conclusions: The issue of OA journals as compared with traditional subscription-based journals is highly debated among stakeholders: library administrators facing financial restrictions, authors seeking to locate the best outlet for their research, publishers wishing to increase their revenues by offering journals with wider appeal. Against this background, factors such as the quest for alternatives to high-cost business models, investments in setting up institutional repositories hosting the published versions of articles and efforts to overcome copyright barriers and gain free access to scientific literature are all crucial.
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http://dx.doi.org/10.1186/1756-9966-32-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618298PMC
January 2013

Computing sources of epileptic discharges using the novel BMA approach: comparison with other distributed inverse solution methods.

Clin EEG Neurosci 2013 Jan 17;44(1):3-15. Epub 2012 Dec 17.

Havana Institute of Neurology and Neurosurgery, Havana, Cuba.

Electroencephalography (EEG) source localization in epileptology continues to be a challenge for neuroscientists. A number of inverse solution (IS) methodologies have been proposed to solve this problem, and their advantages and limitations have been described. In the present work, a previously developed IS approach called Bayesian model averaging (BMA) is introduced in clinical practice in order to improve the localization accuracy of epileptic discharge sources. For this study, 31 patients with the diagnosis of partial epilepsies were studied: 14 had benign childhood epilepsy with centrotemporal spikes and 17 had temporal lobe epilepsy (TLE). The underlying epileptic sources were localized using the BMA approach, and the results were compared with those expected from the clinical diagnosis. Additional comparisons with results obtained from 3 of the most commonly used distributed IS methods for these purposes (minimum norm [MN], weighted minimum norm [WMN], and low-resolution electromagnetic tomography [LORETA]) were carried out in terms of source localization accuracy and spatial resolutions. The BMA approach estimated discharge sources that were consistent with the clinical diagnosis, and this method outperformed LORETA, MN, and WMN in terms of both localization accuracy and spatial resolution. The BMA was able to localize deeper generators with high accuracy. In conclusion, the BMA methodology has a great potential for the noninvasive accurate localization of epileptic sources, even those located in deeper structures. Therefore, it could be a promising tool for clinical practice in epileptology, although additional studies in other types of epileptic syndromes are necessary.
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http://dx.doi.org/10.1177/1550059412451706DOI Listing
January 2013

Coenzyme Q metabolism is disturbed in high fat diet-induced non-alcoholic fatty liver disease in rats.

Int J Mol Sci 2012 2;13(2):1644-57. Epub 2012 Feb 2.

Department of Cell Biology and Neuroscience, National Institute of Health, Rome 00161, Italy; E-Mail:

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.
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http://dx.doi.org/10.3390/ijms13021644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291983PMC
July 2015

Laser-assisted lipolysis for knee remodelling: a prospective study in 30 patients.

J Cosmet Laser Ther 2012 Apr;14(2):59-66

Instituto Médico Láser, Madrid, Spain.

Background: Unsightly fat knees are a frustrating aesthetic deformity exacerbated by genetic predisposition and resistance to diet. This article reports our experience with laser-assisted lipolysis (LAL) in knee remodelling.

Methods: A total of 30 patients were treated for unsightly fat knees with LAL. The 924/975-nm diode laser used in this study consists of two lasers, one emitting at 924 nm and another at 975 nm. Previous mathematical modelling suggested that 0.1 kJ was required in order to destroy 1 ml of fat, in dual emission mode at 924/975 nm. Patients were asked to fill out a satisfaction questionnaire. Ultrasound was used to measure the fat thickness pre-and post-operatively.

Results: Other than one patient who developed mild hyperpigmentation that disappeared after 2 months, there were no complications in the series. Pain during the anaesthesia and discomfort after the procedure were minimal. Return to normal activities never took longer than 2 days and mean downtime was 0.92 days. Of the 30 patients, 29 would recommend this treatment. Overall satisfaction was high with both patients and investigators and was validated by ultrasound measurements demonstrating a systematic decrease in fat thickness.

Conclusion: LAL in knee remodelling is a safe and reproducible technique, particularly appreciated by patients. The procedure allows for a reduction in the amount of adipose deposits while providing concurrent skin contraction.
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http://dx.doi.org/10.3109/14764172.2012.670248DOI Listing
April 2012

Phospholipase A2 mediates apolipoprotein-independent uptake of chylomicron remnant-like particles by human macrophages.

Int J Vasc Med 2012 21;2012:501954. Epub 2011 Aug 21.

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

Apolipoprotein E-receptor-mediated pathways are the main routes by which macrophages take up chylomicron remnants, but uptake may also be mediated by receptor-independent routes. To investigate these mechanisms, triacylglycerol (TG) accumulation induced by apolipoprotein-free chylomicron remnant-like particles (CRLPw/o) in human monocyte-derived macrophages was evaluated. Macrophage TG content increased about 5-fold after incubation with CRLPw/o, and this effect was not reduced by the inhibition of phagocytosis, macropinocytosis, apolipoprotein E function, or proteoglycan bridging. The role of lipases, including lipoprotein lipase, cholesteryl ester hydrolase, and secretory (sPLA2) and cytosolic phospholipase A2, was studied using [(3)H]TG-labelled CRLPw/o. Total cell radioactivity after incubation with [(3)H]TG CRLPw/o was reduced by 15-30% by inhibitors of lipoprotein lipase and cholesteryl ester hydrolase and by about 45% by inhibitors of sPLA2 and cytosolic PLA(2) . These results suggest that macrophage lipolytic enzymes mediate the internalization of postprandial TG-rich lipoproteins and that sPLA(2) and cytosolic PLA2, play a more important role than extracellular lipoprotein lipase-mediated TG hydrolysis.
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http://dx.doi.org/10.1155/2012/501954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160105PMC
November 2011

Biobank networking: the European network initiative and the italian participation.

Biopreserv Biobank 2011 Jun;9(2):175-9

1 Information Technology Unit, Istituto Superiore di Sanità , Rome, Italy .

The evolution of the Biobanking and Biomolecular Resources Infrastructure, planned as a federated network of biological resources centers including all types of repositories of biological materials of human origin, toward a legal consortium of European Union Member States is described. The inception of Biobanking and Biomolecular Resources Infrastructure gave a strong impetus to the reorganization of the Italian biobanks both with the formation of structured specific networks of disease-oriented biobanks as well as with the establishment of biobank networks with a regional constituency. This complex articulation requires a strong central coordination that the Health Minister entrusted to the Istituto Superiore di Sanità.
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http://dx.doi.org/10.1089/bio.2011.0004DOI Listing
June 2011

High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway.

Lipids Health Dis 2011 Apr 19;10:60. Epub 2011 Apr 19.

Department of Cellular Biology and Neuroscience, Istituto Superiore Sanità, Rome, Italy.

Background: Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated.

Methods And Results: After feeding rats a standard low fat diet (control) or a high fat diet (57% metabolisable energy as fat) for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS), the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group.

Conclusions: These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.
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http://dx.doi.org/10.1186/1476-511X-10-60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096990PMC
April 2011

Neutrophil unsaturated fatty acid release by GM-CSF is impaired in cystic fibrosis.

Lipids Health Dis 2010 Nov 8;9:129. Epub 2010 Nov 8.

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 199-00161 Roma, Italy.

Dysregulated inflammation in cystic fibrosis (CF) is attributed to an altered production of inflammatory mediators derived from polyunsaturated lipids. In comparison to the arachidonic acid (AA) cascade, little is known about the modulation of docosahexaenoic acid (DHA) membrane release. We compared data on neutrophil DHA- and AA- release from both control (CT) and patients with CF using [3H]AA or [14C]DHA as a markers for, respectively, AA and DHA- release. Granulocyte-macrophage-colony stimulating factor stimulated DHA release from CT, but not CF, neutrophils. Comparison showed that both [14C]DHA and [3H]AA liberated after stimulation was higher in CT than in CF neutrophils. Since bioactive mediators derived from DHA are resolving factors and those derived from AA are both pro- and anti- inflammatory, these results suggest that CF is associated with a reduction of the release of PUFA-precursors of lipooxygenated resolving mediators. This leads to the hypothesis that defects in the resolving factors production could contribute to the inflammatory dysregulated processes in CF. Furthermore, the methodology used may help to improve knowledge on the regulation and resolution of inflammation.
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http://dx.doi.org/10.1186/1476-511X-9-129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988788PMC
November 2010

Anatomic study of the abductor pollicis longus: a source for grafting material of the hand.

Clin Orthop Relat Res 2010 May 4;468(5):1305-9. Epub 2009 Sep 4.

Plastic Surgery Department, Hospital La Paz, Paseo de la Castellana 261, 4 feminine planta, Madrid 28046, Spain.

Interposition grafting material is used frequently to treat osteoarthritis of the base of the thumb or tendinous and ligamentous injuries of the hand. The observation of duplicated tendons in the first dorsal compartment of the hand prompted us to explore the possibility of using the accessory abductor pollicis longus (AAPL) tendon as grafting material. Based on dissections of 78 cadaveric upper limbs, we describe the number of tendons in the first dorsal compartment of the hand, the number of muscle bellies, their innervation, their insertion site, and the tendon dimensions to determine whether the AAPL can be considered a true tendon. The AAPL was present in 85% of the hands. Average length, width, and thickness (in millimeters) of the APL were of 69.3, 5.2, and 2.1, respectively. Average length, width, and thickness (in millimeters) of the AAPL were of 69.2, 3.3, and 1.6, respectively. No differences in dimension of the tendons were found between the APL and the AAPL. The dimensions of the tendinous portion of the AAPL are similar to those of the APL and can be considered a true tendon. When present, the AAPL is a suitable source of local grafting material.
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http://dx.doi.org/10.1007/s11999-009-1059-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853646PMC
May 2010

Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease: is there a role for dietary coenzyme Q?

J Appl Physiol (1985) 2009 Sep 16;107(3):707-17. Epub 2009 Jul 16.

Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 0TU, United Kingdom.

The overproduction of very-low-density lipoprotein (VLDL) is a characteristic feature of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to use a high-fat diet-induced model of NAFLD in rats to investigate 1) the influence of the disease on hepatic VLDL processing in the endoplasmic reticulum and 2) the potential modulatory effects of dietary coenzyme Q (CoQ). Rats were fed a standard low-fat diet (control) or a diet containing 35% fat (57% metabolizable energy). After 10 wk, high-fat diet-fed animals were divided into three groups: the first group was given CoQ9 (30 mg*kg body wt(-1)*day(-1) in 0.3 ml olive oil), the second group was given olive oil (0.3 ml/day) only, and the third group received no supplements. Feeding (3 high-fat diets and the control diet) was then continued for 8 wk. In all high-fat diet-fed groups, the content of triacylglycerol (TG) and cholesterol in plasma VLDL, the liver, and liver microsomes was increased, hepatic levels of apolipoprotein B48 were raised, and the activities of microsomal TG transfer protein and acyl CoA:cholesterol acyltransferase were reduced. These findings provide new evidence indicating that VLDL assembly and the inherent TG transfer to the endoplasmic reticulum are altered in NAFLD and suggest a possible explanation for both the overproduction of VLDL associated with the condition and the disease etiology itself. Dietary CoQ caused significant increases in apolipoprotein B mRNA and microsomal TG levels and altered the phospholipid content of microsomal membranes. These changes, however, may not be beneficial as they may lead to the secretion of larger, more atherogenic VLDL.
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http://dx.doi.org/10.1152/japplphysiol.00297.2009DOI Listing
September 2009

Induction of non-alcoholic fatty liver disease and insulin resistance by feeding a high-fat diet in rats: does coenzyme Q monomethyl ether have a modulatory effect?

Nutrition 2009 Nov-Dec;25(11-12):1157-68. Epub 2009 Jul 9.

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy.

Objective: The aim of this study was to investigate the development of non-alcoholic fatty liver disease (NAFLD) in response to a high-fat diet in rats and to test the hypothesis that dietary coenzyme Q monomethyl ether (CoQme) has antisteatogenic effects.

Methods: Rats were fed a standard low-fat diet (control) for 18 wk or a diet containing 35% fat (57% metabolizable energy) for 10 wk, then divided into three groups for the following 8 wk. One group was given CoQ9me (30mg/kg body weight per day in 0.3mL olive oil: high fat+CoQ9me), the second olive oil (0.3mL/d) only (high fat + olive oil), and the third group received no supplements (high fat).

Results: Insulin levels and the activity of alanine aminotransferase in the plasma were significantly increased in all high-fat diet groups, and the homeostasis model assessment of insulin resistance indicated insulin resistance. Triacylglycerol concentrations in whole plasma and in very low-density lipoprotein and low-density lipoprotein fractions were also raised. Liver histology showed lipid accumulation in animals fed the high-fat diets, and liver triacylglycerol levels were increased (2.5- to 3-fold) in all high-fat diet groups. These effects were not changed by the administration of CoQ9me.

Conclusions: Rats fed a diet with 57% energy from fat showed insulin resistance, hypertriglyceridemia, increased very low-density lipoprotein production, hepatic steatosis, and liver damage, and thus provide a good model for the early stages of NAFLD. Dietary CoQ9me, however, did not ameliorate the damaging effects of the high-fat diet.
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http://dx.doi.org/10.1016/j.nut.2009.02.009DOI Listing
February 2010