3D printable electroconductive gelatin‑hyaluronic acid materials containing polypyrrole nanoparticles for electroactive tissue engineering

Electrically conductive bio-scaffolds are explored in the field of tissue engineering (TE) as a solution to address the clinical need of electroactive tissues, finding applications in nervous, cardiac, and spinal cord injury repair. In this work, we synthesise polypyrrole nanoparticles (PPy NP) via the mini-emulsion method with further combination with a gelatin/hyaluronic acid (HA) hydrogel to create electroconductive Gel:HA:PPy-NP TE scaffolds. Electroconductive Gel:HA:PPy-NP scaffolds possess excellent mechanical properties at 1.08 ± 0.26 MPa, closely matching the reported mechanical performance of the spinal cord. Scaffolds were designed with controlled porosity of 526.2 ± 74.6â 403.9 ± 57.4 μm, and conductivities of 4.3 à 10 â 6 ± 1.1 à 10 â 6 S.cm â 1 were reached. Rheological studies show that prior to lyophilisation, the Gel:HA:PPy-NP hydrogels display a shear-thinning behaviour. These gels were subsequently 3D printed into predefined 2 layer lattice geometries and displayed excellent post-printing shape fidelity. In vitro studies show that the Gel:HA:PPy-NP scaffolds are cytocompatible with mesenchymal stem cells and neuronal stem cells and display encouraging cell attachment and proliferation profiles. Based on these results, the incorporation of PPy NPs into Gel:HA biomaterial scaffolds enhances the conductive capabilities of the material, while showcasing biocompatible behaviour with cell cultures. Hence, Gel:HA:PPy-NP scaffolds are a promising TE option for stimulating regeneration following nervous tissue injury.The authors would like to thank the funding provided by the Irish Research Council through the Irish Research Council Enterprise Partnership Scheme with Johnson and Johnson (EPSPG/2020/78), as well as the Irish Fulbright Commission

Electroconductive PEDOT nanoparticle integrated scaffolds for spinal cord tissue repair

Background: Hostile environment around the lesion site following spinal cord injury (SCI) prevents the re-establishment of neuronal tracks, thus significantly limiting the regenerative capability. Electroconductive scaffolds are emerging as a promising option for SCI repair, though currently available conductive polymers such as polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) present poor biofunctionality and biocompatibility, thus limiting their effective use in SCI tissue engineering (TE) treatment strategies. Methods: PEDOT NPs were synthesized via chemical oxidation polymerization in miniemulsion. The conductive PEDOT NPs were incorporated with gelatin and hyaluronic acid (HA) to create gel:HA:PEDOT-NPs scaffolds. Morphological analysis of both PEDOT NPs and scaffolds was conducted via SEM. Further characterisation included dielectric constant and permittivity variances mapped against morphological changes after crosslinking, Young’s modulus, FTIR, DLS, swelling studies, rheology, in-vitro, and in-vivo biocompatibility studies were also conducted. Results: Incorporation of PEDOT NPs increased the conductivity of scaffolds to 8.3 × 10–4 ± 8.1 × 10–5 S/cm. The compressive modulus of the scaffold was tailored to match the native spinal cord at 1.2 ± 0.2 MPa, along with controlled porosity. Rheological studies of the hydrogel showed excellent 3D shear-thinning printing capabilities and shape fidelity post-printing. In-vitro studies showed the scaffolds are cytocompatible and an in-vivo assessment in a rat SCI lesion model shows glial fibrillary acidic protein (GFAP) upregulation not directly in contact with the lesion/implantation site, with diminished astrocyte reactivity. Decreased levels of macrophage and microglia reactivity at the implant site is also observed. This positively influences the re-establishment of signals and initiation of healing mechanisms. Observation of axon migration towards the scaffold can be attributed to immunomodulatory properties of HA in the scaffold caused by a controlled inflammatory response. HA limits astrocyte activation through its CD44 receptors and therefore limits scar formation. This allows for a superior axonal migration and growth towards the targeted implantation site through the provision of a stimulating microenvironment for regeneration. Conclusions: Based on these results, the incorporation of PEDOT NPs into Gel:HA biomaterial scaffolds enhances not only the conductive capabilities of the material, but also the provision of a healing environment around lesions in SCI. Hence, gel:HA:PEDOT-NPs scaffolds are a promising TE option for stimulating regeneration for SCI.The authors would like to thank the funding provided by the Irish Research Council through the Irish Research Council Enterprise Partnership Scheme with Johnson and Johnson (EPSPG/2020/78), as well as the Irish Fulbright Commission

Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial

Evidence suggests that the norepinephrine system represents an important treatment target for alcohol dependence (AD) and the α1-blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α1-blocker doxazosin demonstrates a more favorable pharmacokinetic profile than prazosin, but has never been studied for AD. A double-blind placebo-controlled randomized clinical trial was conducted in AD individuals seeking outpatient treatment. Doxazosin or matched placebo was titrated to 16 mg/day (or maximum tolerable dose). Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. Family history density of alcoholism (FHDA), severity of AD and gender were a priori moderators. Forty-one AD individuals were randomized, 30 (doxazosin = 15) completed the treatment phase and 28 (doxazosin = 14) also completed the follow-up. There were no significant differences between groups on DPW and HDD per week. With FHDA as a moderator, there were significant FHDA × medication interactions for both DPW (pcorrected = 0.001, d = 1.18) and HDD (pcorrected = 0.00009, d = 1.30). Post hoc analyses revealed that doxazosin significantly reduced alcohol drinking in AD patients with high FHDA and by contrast increased drinking in those with low FHDA. Doxazosin may be effective selectively in AD patients with high FHDA. This study provides preliminary evidence for personalized medicine using α1-blockade to treat AD. However, confirmatory studies are required

Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach

Peripheral nerve growth within a hydrogel microchannel scaffold supported by a kink‐resistant conduit

Nerve repair in several mm‐long nerve gaps often requires an interventional technology. Microchannel scaffolds have proven effective for bridging nerve gaps and guiding axons in the peripheral nervous system (PNS). Nonetheless, fabricating microchannel scaffolds at this length scale remains a challenge and/or is time consuming and cumbersome. In this work, a simple computer‐aided microdrilling technique was used to fabricate 10 mm‐long agarose scaffolds consisting of 300 µm‐microchannels and 85 µm‐thick walls in less than an hour. The agarose scaffolds alone, however, did not exhibit adequate stiffness and integrity to withstand the mechanical stresses during implantation and suturing. To provide mechanical support and enable suturing, poly caprolactone (PCL) conduits were fabricated and agarose scaffolds were placed inside. A modified salt‐leaching technique was developed to introduce interconnected porosity in PCL conduits to allow for tuning of the mechanical properties such as elastic modulus and strain to failure. It was shown that the PCL conduits were effective in stabilizing the agarose scaffolds in 10 mm‐long sciatic nerve gaps of rats for at least 8 weeks. Robust axon ingress and Schwann cell penetration were observed within the microchannel scaffolds without using growth factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3392–3399, 2017.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139110/1/jbma36186_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139110/2/jbma36186.pd

Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

Background: Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. Methods: This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Results: Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. Conclusion: These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use

¿Cómo convertirse en un ciudadano científico?

La Ciencia Ciudadana nos brinda una oportunidad de conocer más a la naturaleza, aprender sobre ella, contribuir a la ciencia, compartir nuestras observaciones y motivar a otras personas a interesarse por la biodiversidad que nos rodea. Además, la ciencia ciudadana puede contribuir a la elaboración de políticas públicas y leyes, y fomentar la participación de la sociedad en la toma de decisiones. ¡Hay muchas razones para participar en proyectos de Ciencia Ciudadana!Fil: Arbetman, Marina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Barahona Segovia, Rodrigo M.. Universidad de Los Lagos; ChileFil: Burgos, Adriana. Jardin Botánico Carlos Thays; ArgentinaFil: Aparecida Gobatto, Alexandra. Instituto de Pesquisas Jardim Botânico do Rio de Janeiro; BrasilFil: Koffler, Sheina. Universidade de Sao Paulo; BrasilFil: Queiroz Souza, Caren. Universidade Federal da Bahia; Brasi

FIT Count Brasil: monitoramento de visitantes florais por contagem.

A Série de livros "Ciência Cidadã" tem como objetivo apresentar ao público diferentes questões científicas que podem ser trabalhadas com o auxílio de cientistas cidadãos e motivar diferentes pessoas (como você, por exemplo) a atuarem como cientistas cidadãos. No presente livro, apresentamos o protocolo intitulado "FIT COUNT: contagem cronometrada de visitantes florais"

Open Database of Epileptic EEG with MRI and Postoperational Assessment of Foci—a Real World Verification for the EEG Inverse Solutions

This paper introduces a freely accessible database http://eeg.pl/epi, containing 23 datasets from patients diagnosed with and operated on for drug-resistant epilepsy. This was collected as part of the clinical routine at the Warsaw Memorial Child Hospital. Each record contains (1) pre-surgical electroencephalography (EEG) recording (10–20 system) with inter-ictal discharges marked separately by an expert, (2) a full set of magnetic resonance imaging (MRI) scans for calculations of the realistic forward models, (3) structural placement of the epileptogenic zone, recognized by electrocorticography (ECoG) and post-surgical results, plotted on pre-surgical MRI scans in transverse, sagittal and coronal projections, (4) brief clinical description of each case. The main goal of this project is evaluation of possible improvements of localization of epileptic foci from the surface EEG recordings. These datasets offer a unique possibility for evaluating different EEG inverse solutions. We present preliminary results from a subset of these cases, including comparison of different schemes for the EEG inverse solution and preprocessing. We report also a finding which relates to the selective parametrization of single waveforms by multivariate matching pursuit, which is used in the preprocessing for the inverse solutions. It seems to offer a possibility of tracing the spatial evolution of seizures in time