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Microstructured polymeric fabrics modulating the paracrine activity of adipose-derived stem cells
Get PDFThe deposition of stem cells at sites of injury is a clinically relevant approach to facilitate tissue repair and angiogenesis. However, insufficient cell engraftment and survival require the engineering of novel scaffolds. Here, a regular network of microscopic poly(lactic-co-glycolic acid) (PLGA) filaments was investigated as a promising biodegradable scaffold for human Adipose-Derived Stem Cell (hADSC) tissue integration. Via soft lithography, three different microstructured fabrics were realized where 5 x 5 and 5 x 3 & mu;m PLGA 'warp' and 'weft' filaments crossed perpendicularly with pitch distances of 5, 10 and 20 & mu;m. After hADSC seeding, cell viability, actin cytoskeleton, spatial organization and the secretome were characterized and compared to conventional substrates, including collagen layers. On the PLGA fabric, hADSC re-assembled to form spheroidal-like structures, preserving cell viability and favoring a nonlinear actin organization. Moreover, the secretion of specific factors involved in angiogenesis, the remodeling of the extracellular matrix and stem cell homing was favored on the PLGA fabric as compared to that which occurred on conventional substrates. The paracrine activity of hADSC was microstructure-dependent, with 5 & mu;m PLGA fabric enhancing the expression of factors involved in all three processes. Although more studies are needed, the proposed PLGA fabric would represent a promising alternative to conventional collagen substrates for stem cell implantation and angiogenesis induction
Brucellosis and one health: inherited and future challenges
Get PDFOne Health is the collaborative efforts of multiple disciplines to attain optimal health for people, animals and the environment, a concept that historically owes much to the study of brucellosis, including recent political and ethical considerations. Brucellosis One Health actors include Public Health and Veterinary Services, microbiologists, medical and veterinary practitioners and breeders. Brucellosis awareness, and the correct use of diagnostic, epidemiological and prophylactic tools is essential. In brucellosis, One Health implementation faces inherited and new challenges, some aggravated by global warming and the intensification of breeding to meet growing food demands. In endemic scenarios, disease awareness, stakeholder sensitization/engagement and the need to build breeder trust are unresolved issues, all made difficult by the protean characteristics of this zoonosis. Extended infrastructural weaknesses, often accentuated by geography and climate, are critically important. Capacity-building faces misconceptions derived from an uncritical adoption of control/eradication strategies applied in countries with suitable means, and requires additional reference laboratories in endemic areas. Challenges for One Health implementation include the lack of research in species other than cattle and small ruminants, the need for a safer small ruminant vaccine, the need to fill in the infrastructure gap, the need for realistic capacity-building, the creation of reference laboratories in critical areas, and the stepwise implementation of measures not directly transposed from the so-called developed countries
Comparison of antibacterial activity and cytotoxicity of silver nanoparticles and silver-loaded montmorillonite and saponite
Get PDFAlthough silver nanoparticles are known for their antibacterial activity, little research has been carried out on
what synthesis method provides the most effective particles. In this study, silver nanoparticles were synthesised
via chemical reduction by using silver nitrate as the silver precursor, ascorbic acid as the reducing agent and
sodium citrate as the stabilising agent. The solutions were adjusted to several pH values employing sodium
hydroxide, citric acid or nitric acid. Dynamic light scattering and absorption spectra in the ultraviolet/visible
region characterisation revealed that employing nitric acid to adjust the pH produced more varied and larger
silver particle sizes. Then, silver nanoparticles were supported on montmorillonite and saponite through wet
impregnation or ion exchange methods. Scanning electron microscopy, energy-dispersive X-ray spectroscopy and
transmission electron microscopy characterisation confirmed that silver nanoparticles were successfully loaded
onto the clay minerals. Next, the antibacterial activity of the samples was evaluated against Escherichia coli and
Staphylococcus aureus by determining their minimum inhibitory concentrations and minimum bactericidal concentrations. The free silver nanoparticles did not show any antibacterial activity at 125 mg/L. In contrast, the
silver-loaded samples obtained by wet impregnation and with a higher silver content displayed the strongest
antibacterial effect. Finally, the cytotoxicity of the samples was determined in GM07492-A cell line by using an
XTT colorimetric assay. The calculated IC50 values revealed that the supported silver nanoparticles were barely
toxic. Thus, the silver-loaded clay minerals obtained here are promising antibacterial materials with a high-grade
safety profile
CC-Chemokine receptor-2 expression in osteoblasts contributes to cartilage and bone damage during post-traumatic osteoarthritis
No full textIn osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether Ccr2 osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible Ccr2 inactivation in Collagen1 & alpha;-expressing cells to obtain osteoblasts lacking Ccr2 (CCR2-Col1 & alpha;KO). We stimulated PTOA changes in CCR2-Col1 & alpha;KO and CCR2+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-Ccr2 inactivation delayed articular cartilage damage and matrix degeneration compared to CCR2+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1 & alpha;-Ccr2 deletion led to less evident improvements. Osteoblast-Ccr2 deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that Ccr2 expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues
Multiqubit time-varying quantum channels for NISQ-era superconducting quantum processors
No full textTime-varying quantum channels (TVQCs) have been proposed as a model to include fluctuations of the relaxation (T1) and dephasing times (T2). In previous works, realizations of multiqubit TVQCs have been assumed to be equal for all the qubits of an error correction block, implying that the random variables that describe the fluctuations of T1 and T2 are block-to-block uncorrelated but qubit-wise perfectly correlated for the same block. In this article, we perform a correlation analysis of the fluctuations of the relaxation times of five multiqubit quantum processors. Our results show that it is reasonable to assume that the fluctuations of the relaxation and dephasing times of superconducting qubits are local to each of the qubits of the system. Based on these results, we discuss the multiqubit TVQCs when the fluctuations of the decoherence parameters for an error correction block are qubit-wise uncorrelated (as well as from block-to-block), a scenario we have named the fast time-varying quantum channel (FTVQC). Furthermore, we lower-bound the quantum capacity of general FTVQCs based on a quantity we refer to as the ergodic quantum capacity. Finally, we use numerical simulations to study the performance of quantum error correction codes when they operate over FTVQCs
Retention of newly graduated registered nurses in the hospital setting: A systematic review
Get PDFBackground: There is a gap in the literature on identifying and describing effective interventions for the retention of newly graduated registered nurses in hospital set-tings. To the best of our knowledge, no systematic review has been conducted on this issue.Aim: To identify effective interventions that promote the retention of newly gradu-ated registered nurses in the hospital setting and their components.Design: A systematic review was conducted according to PRISMA 2020 Statement.Methods: Information derived from the PubMed, CINAHL, Scopus, PsycINFO and Cochrane Library databases was reviewed, for the period January 2012–October 2022. Screening, data extraction and quality appraisal were conducted independently by two reviewers. The Joanna Briggs Institute Critical Appraisal tools were used for descriptive, quasi-experimental and cohort studies. Disagreements between the two reviewers were resolved through discussion.Results: Following the critical appraisal, nine studies were included. The evidence re-veals the heterogeneity of programmes developed in the hospital context to promote the retention of newly graduated registered nurses, clarifies the three competencies to be addressed (core, cross-cutting and specific), their components (programme de-velopment framework, duration, content and support components), and shows sig-nificant improvements after their implementation.Conclusions: This systematic review identifies that either nurse residency or individu-alised mentoring programmes, lasting 1 year, and multi-component, addressing core and specific competencies and including preceptor or mentor components seem to be the most comprehensive and effective in promoting the retention of new nurses in the hospital setting.Relevance to Clinical Practice: The knowledge provided by this review will contrib-ute to developing and implementing more effective and context-specific strategies directed at retaining newly graduated registered nurses and subsequently enhancing patient safety and healthcare costs.No Patient or Public Contribution: Given the study design and focus
El abandono escolar de adolescentes en España
Get PDFEl abandono escolar sigue siendo una realidad presente entre los adolescentes de
la sociedad actual en la que la familia y la escuela ocupan un papel prioritario, tanto
positiva como negativamente. Tanto es así que datos recientes revelan que España es, en
el año 2021, el sexto país con mayor tasa de abandono escolar. Tras el estudio de las
características del adolescente actual, los riesgos a los que se expone, las causas del
abandono y las diferencias entre las Comunidades Autónomas de España, se presenta
una propuesta de intervención para prevenir y hacer frente al abandono escolar,
sugiriendo una serie de acciones o recomendaciones que pueden llevarse a cabo desde la
familia y la escuela para prevenir o mitigar dicho fenómeno.School dropout continues to be a reality among adolescents in today's society in
which the family and the school play a priority role, both positively and negatively. So
much so that recent data reveal that Spain is, in the year 2021, the sixth country with the
highest school dropout rate. After studying the characteristics of today's adolescents, the
risks to which they are exposed, the causes of dropout and the differences between the
Autonomous Communities of Spain, is presented a proposal for intervention to prevent
and deal with school dropout, suggesting a series of actions or recommendations that
can be carried out by the family and the school to prevent or mitigate this phenomenon
An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration
Get PDFDuring bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 mu g/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses
Stabilization of 14-3-3 protein-protein interactions with Fusicoccin-A decreases alpha-synuclein dependent cell-autonomous death in neuronal and mouse models
No full textSynucleinopathies are a group of neurodegenerative diseases without effective treatment characterized by the abnormal aggregation of alpha-synuclein (aSyn) protein. Changes in levels or in the amino acid sequence of aSyn (by duplication/triplication of the aSyn gene or point mutations in the encoding region) cause familial cases of synucleinopathies. However, the specific molecular mechanisms of aSyn-dependent toxicity remain unclear. Increased aSyn protein levels or pathological mutations may favor abnormal protein-protein interactions (PPIs) that could either promote neuronal death or belong to a coping response program against neurotoxicity. Therefore, the identification and modulation of aSyn-dependent PPIs can provide new therapeutic targets for these diseases. To identify aSyn-dependent PPIs we performed a proximity biotinylation assay based on the promiscuous biotinylase BioID2. When expressed as a fusion protein, BioID2 biotinylates by proximity stable and transient interacting partners, allowing their identification by streptavidin affinity purification and mass spectrometry. The aSyn interactome was analyzed using BioID2-tagged wild-type (WT) and pathological mutant E46K aSyn versions in HEK293 cells. We found the 14-3-3 epsilon isoform as a common protein interactor for WT and E46K aSyn. 14-3-3 epsilon correlates with aSyn protein levels in brain regions of a transgenic mouse model overexpressing WT human aSyn. Using a neuronal model in which aSyn cell-autonomous toxicity is quantitatively scored by longitudinal survival analysis, we found that stabilization of 14-3-3 protein-proteins interactions with Fusicoccin-A (FC-A) decreases aSyn-dependent toxicity. Furthermore, FC-A treatment protects dopaminergic neuronal somas in the substantia nigra of a Parkinson's disease mouse model. Based on these results, we propose that the stabilization of 14-3-3 epsilon interaction with aSyn might reduce aSyn toxicity, and highlight FC-A as a potential therapeutic compound for synucleinopathies
Gene therapy restores the transcriptional program of hematopoietic stem cells in Fanconi anemia
No full textClinical trials have shown that lentiviral-mediated gene therapy can ameliorate bone marrow failure (BMF) in nonconditioned Fanconi anemia (FA) patients resulting from the proliferative advantage of corrected FA hematopoietic stem and progenitor cells (HSPC). However, it is not yet known if gene therapy can revert affected molecular pathways in diseased HSPC. Single-cell RNA sequencing was performed in chimeric populations of corrected and uncorrected HSPC co-existing in the BM of gene therapy-treated FA patients. Our study demonstrates that gene therapy reverts the transcriptional signature of FA HSPC, which then resemble the transcriptional program of healthy donor HSPC. This includes a down-regulated expression of TGF-ß and p21, typically up-regulated in FA HSPC, and upregulation of DNA damage response and telomere maintenance pathways. Our results show for the first time the potential of gene therapy to rescue defects in the HSPC transcriptional program from patients with inherited diseases; in this case, in FA characterized by BMF and cancer predisposition