12 research outputs found
Robust fabrication of electrospun-like polymer mats to direct cell behaviour
Currently, cell culture systems that include nanoscale topography are widely used in order to provide cells additional cues closer to the in vivo environment, seeking to mimic the natural extracellular matrix. Electrospinning is one of the most common techniques to produce nanofiber mats. However, since many sensitive parameters play an important role in the process, a lack of reproducibility is a major drawback. Here we present a simple and robust methodology to prepare reproducible electrospun-like samples. It consists of a polydimethylsiloxane mold reproducing the fiber pattern to solvent-cast a polymer solution and obtain the final sample. To validate this methodology, poly( L-lactic) acid ( PLLA) samples were obtained and, after characterisation, bioactivity and ability to direct cell response were assessed. C2C12 myoblasts developed focal adhesions on the electrospun-like fibers and, when cultured under myogenic differentiation conditions, similar differentiation levels to electrospun PLLA fibers were obtained.The support of ERC through HealInSynergy (306990) and FPU program AP2009-3626 is acknowledged.Ballester BeltrĂĄn, J.; Lebourg., MM.; Capella MonsonĂs, H.; DĂaz Lantada, A.; SalmerĂłn SĂĄnchez, M. (2014). Robust fabrication of electrospun-like polymer mats to direct cell behaviour. Biofabrication. 6(3). https://doi.org/10.1088/1758-5082/6/3/035009S6
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Guidelines for the LiâFraumeni and heritable TP53 -related cancer syndromes
Abstract: Fifty years after the recognition of the LiâFraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years
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Guidelines for the LiâFraumeni and heritable TP53 -related cancer syndromes
Abstract: Fifty years after the recognition of the LiâFraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years
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Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome
Abstract: PTEN hamartoma tumour syndrome is a diverse multi-system disorder predisposing to the development of hamartomatous growths, increasing risk of breast, thyroid, renal cancer, and possibly increasing risk of endometrial cancer, colorectal cancer and melanoma. There is no international consensus on cancer surveillance in PHTS and all current guidelines are based on expert opinion. A comprehensive literature review was undertaken and guidelines were developed by clinicians with expertise from clinical genetics, gynaecology, endocrinology, dermatology, radiology, gastroenterology and general surgery, together with affected individuals and their representatives. Recommendations were put forward for surveillance for breast, thyroid and renal cancers. Limited recommendations were developed for other sites including endometrial, colon and skin. The proposed cancer surveillance recommendations for PHTS require a coordinated multidisciplinary approach and significant patient commitment. The evidence base for cancer surveillance in this guideline are limited, emphasising the need for prospective evaluation of the effectiveness of surveillance in the PHTS population
Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.
Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de EconomĂa y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de BioinformĂĄtica ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and lowâmiddle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of âsingle-useâ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for lowâmiddle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both highâ and lowâmiddleâincome countries
Interpreting molecular similarity between patients as a determinant of disease comorbidity relationships
International audienceComorbidity is a medical condition attracting increasing attention in healthcare and biomedical research. Little is known about the involvement of potential molecular factors leading to the emergence of a specific disease in patients affected by other conditions. We present here a disease interaction network inferred from similarities between patients' molecular profiles, which significantly recapitulates epidemiologically documented comorbidities. Furthermore, we identify disease patient-subgroups that present different molecular similarities with other diseases, some of them opposing the general tendencies observed at the disease level. Analyzing the generated patient-subgroup network, we identify genes involved in such relations, together with drugs whose effects are potentially associated with the observed comorbidities. All the obtained associations are available at the disease PERCEPTION portal (http://disease-perception.bsc.es)
The Few Who Made It : Commercially and Clinically Successful Innovative Bone Grafts
Bone reconstruction techniques are mainly based on the use of tissue grafts and artificial scaffolds. The former presents well-known limitations, such as restricted graft availability and donor site morbidity, while the latter commonly results in poor graft integration and fixation in the bone, which leads to the unbalanced distribution of loads, impaired bone formation, increased pain perception, and risk of fracture, ultimately leading to recurrent surgeries. In the past decade, research efforts have been focused on the development of innovative bone substitutes that not only provide immediate mechanical support, but also ensure appropriate graft anchoring by, for example, promotingde novobone tissue formation. From the countless studies that aimed in this direction, only few have made the big jump from the benchtop to the bedside, whilst most have perished along the challenging path of clinical translation. Herein, we describe some clinically successful cases of bone device development, including biological glues, stem cell-seeded scaffolds, and gene-functionalized bone substitutes. We also discuss the ventures that these technologies went through, the hindrances they faced and the common grounds among them, which might have been key for their success. The ultimate objective of this perspective article is to highlight the important aspects of the clinical translation of an innovative idea in the field of bone grafting, with the aim of commercially and clinically informing new research approaches in the sector
Migratory Preferences of Humpback Whales Between Feeding and Breeding Grounds in the Eastern South Pacific
Latitudinal preferences within the breeding range have been suggested for Breeding Stock G humpback whales that summer in different feeding areas of the eastern South Pacific. To address this hypothesis, humpback whales photo-identified from the Antarctic Peninsula and the Fueguian Archipelago (southern Chile) were compared with whales photo-identified from lower latitudes extending from northern Peru to Costa Rica. This comparison was performed over a time span that includes 18 austral seasons. A total of 238 whales identified from the Antarctic Peninsula and 25 whales from the Fueguian Archipelago were among those photo-identified at the breeding grounds. Our findings showed that humpback whales from each feeding area were resighted unevenly across the breeding grounds, which suggests a degree of spatial structuring in the migratory pathway. Humpback whales that feed at the Antarctic Peninsula were more likely to migrate to the southern breeding range between northern Peru and Colombia, whereas whales that feed at the Fueguian Archipelago were more likely to be found in the northern range of the breeding ground off Panama. Further photo-identification efforts and genetic sampling from poorly sampled or unsampled areas are recommended to confirm these reported connectivity patterns