Zweifach-Fung Microfluidic Device for Efficient Microparticle Separation: Cost-Effective Fabrication Using CO2 Laser-Ablated PMMA.

Microfluidic separators play a pivotal role in the biomedical and chemical industries by enabling precise fluid manipulations. Traditional fabrication of these devices typically requires costly cleanroom facilities, which limits their broader application. This study introduces a novel microfluidic device that leverages the passive Zweifach-Fung principle to overcome these financial barriers. Through Lagrangian computational simulations, we optimized an eleven-channel Zweifach-Fung configuration that achieved a perfect 100% recall rate for particles following a specified normal distribution. Experimental evaluations determined 2 mL/h as the optimal total flow rate (TFR), under which the device showcased exceptional performance enhancements in precision and recall for micrometer-sized particles, achieving an overall accuracy of 94% ± 3%. Fabricated using a cost-effective, non-cleanroom method, this approach represents a significant shift from conventional practices, dramatically reducing production costs while maintaining high operational efficacy. The cost of each chip is less than USD 0.90 cents and the manufacturing process takes only 15 min. The development of this device not only makes microfluidic technology more accessible but also sets a new standard for future advancements in the field.

Conductive extracellular matrix derived/chitosan methacrylate/ graphene oxide-pegylated hybrid hydrogel for cell expansion.

Electrical stimulation has emerged as a cornerstone technique in the rapidly evolving field of biomedical engineering, particularly within the realms of tissue engineering and regenerative medicine. It facilitates cell growth, proliferation, and differentiation, thereby advancing the development of accurate tissue models and enhancing drug-testing methodologies. Conductive hydrogels, which enable the conduction of microcurrents in 3D in vitro cultures, are central to this advancement. The integration of high-electroconductive nanomaterials, such as graphene oxide (GO), into hydrogels has revolutionized their mechanical and conductivity properties. Here, we introduce a novel electrostimulation assay utilizing a hybrid hydrogel composed of methacryloyl-modified small intestine submucosa (SIS) dECM (SISMA), chitosan methacrylate (ChiMA), and GO-polyethylene glycol (GO-PEG) in a 3D in vitro culture within a hypoxic environment of umbilical cord blood cells (UCBCs). Results not only demonstrate significant cell proliferation within 3D constructs exposed to microcurrents and early growth factors but also highlight the hybrid hydrogel's physiochemical prowess through comprehensive rheological, morphological, and conductivity analyses. Further experiments will focus on identifying the regulatory pathways of cells subjected to electrical stimulation.

From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules.

The emergence of bacterial resistance to antibiotics poses a global health threat, necessitating innovative solutions. The contemporary challenge lies in bacterial resistance, impacting morbidity, mortality, and global economies. Antimicrobial peptides (AMPs) offer a promising avenue for addressing antibiotic resistance. The Antimicrobial Peptide Database catalogs 3569 peptides from various organisms, representing a rich resource for drug development. Histones, traditionally recognized for their role in nucleosome structures, have gained attention for their extracellular functions, including antimicrobial and immunomodulatory properties. This review aims to thoroughly investigate antimicrobial peptides derived from histones in various organisms, elucidating their mechanisms. In addition, it gives us clues about how extracellular histones might be used in drug delivery systems to fight bacterial infections. This comprehensive analysis emphasizes the importance of histone-derived peptides in developing innovative therapeutic strategies for evolving bacterial challenges.

Redefining vascular repair: revealing cellular responses on PEUU-gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models.

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

Diagnoses of common mental disorders among social workers in Sweden: A register-based cohort study.

BACKGROUND: Little is known about common mental disorders (CMD) diagnoses among social workers, i.e., depression, anxiety, or stress-related disorders. This study aims to examine the risk of CMD among social workers in comparison to other workers and to further investigate differences between men and women and specific occupational titles. METHODS: This register-based cohort study consists of 3,034,304 persons, of which 26,610 were social workers (0.9 % of all workers), aged 30-64 years, living in Sweden in 2015. The risk of diagnosed CMDs was followed up until 2020. Cox regression models were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI), adjusting for sex, birth country, education, and birth year. RESULTS: The participants were followed up by a total of 16,833,742.9 person-years, with an average follow-up of 5.5 years. Social workers, compared to other workers, were at a higher risk of CMD (HR 1.3, 95 % CI 1.2-1.4) after adjustment. The HR was equal, 1.3, for depression (95 % CI 1.2-1.5) and anxiety or stress-related disorder (95 % CI 1.2-1.4). The association between social work and CMD was stronger among men (HR 1.7, 95 % CI 1.6-1.9) compared to women (HR 1.2, 95 % CI 1.1-1.3). Further, men working as assistance analysts had the highest risk among the occupational categories (HR 2.2, 95 % CI 1.2-3.9). LIMITATIONS: CMD diagnoses only included cases treated in secondary care. CONCLUSIONS: Social workers, especially male social workers, had a higher risk of CMD. This deserves attention for future research and interventions aimed at improving the mental health of social workers.

Mapping respiratory syncytial virus fusion protein interactions with the receptor IGF1R and the impact of alanine-scanning mutagenesis on viral infection.

Respiratory syncytial virus (RSV) has two main surface glycoproteins, the attachment glycoprotein (G) and the fusion (F) protein, which together mediate viral entry. Attachment is mediated by the RSV-G protein, while the RSV-F protein makes specific contact with the cellular insulin-like growth factor 1 receptor (IGF1R). This interaction leads to IGF1R activation and initiates a signalling cascade that calls the co-receptor, nucleolin, from the nucleus to the cell surface, where it can trigger viral fusion. We performed molecular docking analysis, which provided a potential set of 35 residues in IGF1R that may be important for interactions with RSV-F. We used alanine-scanning mutagenesis to generate IGF1R mutants and assessed their abundance and maturation, as well as the effect of mutation on RSV infection. We identified several mutations that appear to inhibit IGF1R maturation; but surprisingly, these mutations had no significant effect on RSV infection. This suggests that maturation of IGF1R may not be required for RSV infection. Additionally, we identified one residue, S788, that, when mutated, significantly reduced RSV infection. Further analysis revealed that this mutation disrupted a hydrogen bonding network that may be important for both IGF1R maturation and RSV infection.

Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems.

Understanding metabolic heterogeneity is the key to uncovering the underlying mechanisms of metabolic-related diseases. Current metabolic imaging studies suffer from limitations including low resolution and specificity, and the model systems utilized often lack human relevance. Here, we present a single-cell metabolic imaging platform to enable direct imaging of lipid metabolism with high specificity in various human-derived 2D and 3D culture systems. Through the incorporation of an azide-tagged infrared probe, selective detection of newly synthesized lipids in cells and tissue became possible, while simultaneous fluorescence imaging enabled cell-type identification in complex tissues. In proof-of-concept experiments, newly synthesized lipids were directly visualized in human-relevant model systems among different cell types, mutation status, differentiation stages, and over time. We identified upregulated lipid metabolism in progranulin-knockdown human induced pluripotent stem cells and in their differentiated microglia cells. Furthermore, we observed that neurons in brain organoids exhibited a significantly lower lipid metabolism compared to astrocytes.

Low-cost inertial microfluidic device for microparticle separation: A laser-Ablated PMMA lab-on-a-chip approach without a cleanroom.

Although microparticles are frequently used in chemistry and biology, their effectiveness largely depends on the homogeneity of their particle size distribution. Microfluidic devices to separate and purify particles based on their size have been developed, but many require expensive cleanroom manufacturing processes. A cost-effective, passive microfluidic separator is presented, capable of efficiently sorting and purifying particles spanning the size range of 15 µm to 40 µm. Fabricated from Polymethyl Methacrylate (PMMA) substrates using laser ablation, this device circumvents the need for cleanroom facilities. Prior to fabrication, rigorous optimization of the device's design was carried out through computational simulations conducted in COMSOL Multiphysics. To gauge its performance, chitosan microparticles were employed as a test case. The results were notably promising, achieving a precision of 96.14 %. This quantitative metric underscores the device's precision and effectiveness in size-based particle separation. This low-cost and accessible microfluidic separator offers a pragmatic solution for laboratories and researchers seeking precise control over particle sizes, without the constraints of expensive manufacturing environments. This innovation not only mitigates the limitations tied to traditional cleanroom-based fabrication but also widens the horizons for various applications within the realms of chemistry and biology.

Polyester urethane urea (PEUU) functionalization for enhanced anti-thrombotic performance: advancing regenerative cardiovascular devices through innovative surface modifications.

Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices.

The landscape of the immunoglobulin repertoire in endemic pemphigus foliaceus.

Introduction: Primarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immune response in susceptible individuals. We aimed to provide insights into the immune repertoire of patients with PF living in the endemic region of the disease, compared to healthy individuals from the endemic region and a non-endemic area. Methods: We characterized the B-cell repertoire in i) nontreated patients (n=5); ii) patients under immunosuppressive treatment (n=5); iii) patients in remission without treatment (n=6); and two control groups iv) from the endemic (n=6) and v) non-endemic areas in Brazil (n=4). We used total RNA extracted from peripheral blood mononuclear cells and performed a comprehensive characterization of the variable region of immunoglobulin heavy chain (IGH) in IgG and IgM using next-generation sequencing. Results: Compared to individuals from a different area, we observed remarkably lower clonotype diversity in the B-cell immune repertoire of patients and controls from the endemic area (p < 0.02), suggesting that the immune repertoire in the endemic area is under geographically specific and intense environmental pressure. Moreover, we observed longer CDR3 sequences in patients, and we identified differential disease-specific usage of IGHV segments, including increased IGHV3-30 and decreased IGHV3-23 in patients with active disease (p < 0.04). Finally, our robust network analysis discovered clusters of CDR3 sequences uniquely observed in patients with PF. Discussion: Our results indicate that environmental factors, in addition to disease state, impact the characteristics of the repertoire. Our findings can be applied to further investigation of the environmental factors that trigger pemphigus and expand the knowledge for identifying new targeted and more effective therapies.

wMel Wolbachia alters female post-mating behaviors and physiology in the dengue vector mosquito Aedes aegypti.

Globally invasive Aedes aegypti disseminate numerous arboviruses that impact human health. One promising method to control Ae. aegypti populations is transinfection with Wolbachia pipientis, which naturally infects ~40-52% of insects but not Ae. aegypti. Transinfection of Ae. aegypti with the wMel Wolbachia strain induces cytoplasmic incompatibility (CI), allows infected individuals to invade native populations, and inhibits transmission of medically relevant arboviruses by females. Female insects undergo post-mating physiological and behavioral changes-referred to as the female post-mating response (PMR)-required for optimal fertility. PMRs are typically elicited by male seminal fluid proteins (SFPs) transferred with sperm during mating but can be modified by other factors, including microbiome composition. Wolbachia has modest effects on Ae. aegypti fertility, but its influence on other PMRs is unknown. Here, we show that Wolbachia influences female fecundity, fertility, and re-mating incidence and significantly extends the longevity of virgin females. Using proteomic methods to examine the seminal proteome of infected males, we found that Wolbachia moderately affects SFP composition. However, we identified 125 paternally transferred Wolbachia proteins, but the CI factor proteins (Cifs) were not among them. Our findings indicate that Wolbachia infection of Ae. aegypti alters female PMRs, potentially influencing control programs that utilize Wolbachia-infected individuals.

Genome-Scale Metabolic Reconstruction, Non-Targeted LC-QTOF-MS Based Metabolomics Data, and Evaluation of Anticancer Activity of Cannabis sativa Leaf Extracts.

Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.

Enhancing Wound Healing: A Novel Topical Emulsion Combining CW49 Peptide and Lavender Essential Oil for Accelerated Regeneration and Antibacterial Protection.

Wound healing is a complex process involving blood cells, extracellular matrix, and parenchymal cells. Research on biomimetics in amphibian skin has identified the CW49 peptide from Odorrana grahami, which has been demonstrated to promote wound regeneration. Additionally, lavender essential oil exhibits anti-inflammatory and antibacterial activities. Given these considerations, we propose an innovative emulsion that combines the CW49 peptide with lavender oil. This novel formulation could serve as a potent topical treatment, potentially fostering the regeneration of damaged tissues and providing robust antibacterial protection for skin wounds. This study investigates the physicochemical properties, biocompatibility, and in vitro regenerative capacity of the active components and the emulsion. The results show that the emulsion possesses appropriate rheological characteristics for topical application. Both the CW49 peptide and lavender oil exhibit high viability in human keratinocytes, indicating their biocompatibility. The emulsion induces hemolysis and platelet aggregation, an expected behavior for such topical treatments. Furthermore, the lavender-oil emulsion demonstrates antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Finally, the regenerative potential of the emulsion and its active components is confirmed in a 2D wound model using human keratinocytes. In conclusion, the formulated emulsion, which combines the CW49 peptide and lavender oil, shows great promise as a topical treatment for wound healing. Further research is needed to validate these findings in more advanced in vitro models and in vivo settings, potentially leading to improved wound-care management and novel therapeutic options for patients with skin injuries.

Three-dimensional neuroimmune co-culture system for modeling Parkinson's disease microenvironmentsin vitro.

Parkinson's disease (PD) is a complex and multifaceted neurodegenerative disorder that results from multiple environmental factors and multicellular interactions. Although several PD neuropathologies have been identified and described, the thorough understanding of PD pathophysiology and research has been largely limited by the absence of reliablein vitromodels that truly recapitulate PD microenvironments. Here, we propose a neuroimmune co-culture system that models PD neuropathologies by combining relevant multicellular interactions with environments that mimic the brain. This system is composed of: (i) 3D bioprinted cultures of mature human dopaminergic (DA) neurons grown on extracellular matrix (ECM)-derived scaffolds doped with electroconductive nanostructures, and (ii) a direct co-culture of human astrocytes and differentiated monocytes that models neuroinflammatory responses. When co-cultured in a transwell format, these two compartments recreate relevant multicellular environments that model PD pathologies after exposure to the neurotoxin A53Tα-synuclein. With immunofluorescent staining and gene expression analyses, we show that functional and mature DA 3D networks are generated within our ECM-derived scaffolds with superior performance to standard 2D cultures. Moreover, by analyzing cytokine secretion, cell surface markers, and gene expression, we define a human monocyte differentiation scheme that allows the appearance of both monocyte-derived macrophages and dendritic cell phenotypes, as well as their optimal co-culture ratios with human astrocytes to recreate synergistic neuroinflammatory responses. We show that the combined response of both compartments to A53Tα-synuclein stimulates the formation of intracellularα-synuclein aggregates, induces progressive mitochondrial dysfunction and reactive oxygen species production, downregulates the expression of synaptic, DA, and mitophagy-related genes, and promotes the initiation of apoptotic processes within the DA networks. Most importantly, these intracellular pathologies were comparable or superior to those generated with a rotenone-stimulated 2D control that represents the current standard forin vitroPD models and showed increased resilience towards these neurotoxic insults, allowing the study of disease progression over longer time periods than current models. Taken together, these results position the proposed model as a superior alternative to current 2D models for generating PD-related pathologiesin vitro.

Tailoring Magnetite-Nanoparticle-Based Nanocarriers for Gene Delivery: Exploiting CRISPRa Potential in Reducing Conditions.

Gene delivery has emerged as a promising alternative to conventional treatment approaches, allowing for the manipulation of gene expression through gene insertion, deletion, or alteration. However, the susceptibility of gene delivery components to degradation and challenges associated with cell penetration necessitate the use of delivery vehicles for effective functional gene delivery. Nanostructured vehicles, such as iron oxide nanoparticles (IONs) including magnetite nanoparticles (MNPs), have demonstrated significant potential for gene delivery applications due to their chemical versatility, biocompatibility, and strong magnetization. In this study, we developed an ION-based delivery vehicle capable of releasing linearized nucleic acids (tDNA) under reducing conditions in various cell cultures. As a proof of concept, we immobilized a CRISPR activation (CRISPRa) sequence to overexpress the pink1 gene on MNPs functionalized with polyethylene glycol (PEG), 3-[(2-aminoethyl)dithio]propionic acid (AEDP), and a translocating protein (OmpA). The nucleic sequence (tDNA) was modified to include a terminal thiol group and was conjugated to AEDP's terminal thiol via a disulfide exchange reaction. Leveraging the natural sensitivity of the disulfide bridge, the cargo was released under reducing conditions. Physicochemical characterizations, including thermogravimetric analysis (TGA) and Fourier-transform infrared (FTIR) spectroscopy, confirmed the correct synthesis and functionalization of the MNP-based delivery carriers. The developed nanocarriers exhibited remarkable biocompatibility, as demonstrated by the hemocompatibility, platelet aggregation, and cytocompatibility assays using primary human astrocytes, rodent astrocytes, and human fibroblast cells. Furthermore, the nanocarriers enabled efficient cargo penetration, uptake, and endosomal escape, with minimal nucleofection. A preliminary functionality test using RT-qPCR revealed that the vehicle facilitated the timely release of CRISPRa vectors, resulting in a remarkable 130-fold overexpression of pink1. We demonstrate the potential of the developed ION-based nanocarrier as a versatile and promising gene delivery vehicle with potential applications in gene therapy. The developed nanocarrier is capable of delivering any nucleic sequence (up to 8.2 kb) once it is thiolated using the methodology explained in this study. To our knowledge, this represents the first MNP-based nanocarrier capable of delivering nucleic sequences under specific reducing conditions while preserving functionality.

Multifunctional magnetoliposomes as drug delivery vehicles for the potential treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Therefore, development of novel technologies and strategies to treat PD is a global health priority. Current treatments include administration of Levodopa, monoamine oxidase inhibitors, catechol-O-methyltransferase inhibitors, and anticholinergic drugs. However, the effective release of these molecules, due to the limited bioavailability, is a major challenge for the treatment of PD. As a strategy to solve this challenge, in this study we developed a novel multifunctional magnetic and redox-stimuli responsive drug delivery system, based on the magnetite nanoparticles functionalized with the high-performance translocating protein OmpA and encapsulated into soy lecithin liposomes. The obtained multifunctional magnetoliposomes (MLPs) were tested in neuroblastoma, glioblastoma, primary human and rat astrocytes, blood brain barrier rat endothelial cells, primary mouse microvascular endothelial cells, and in a PD-induced cellular model. MLPs demonstrated excellent performance in biocompatibility assays, including hemocompatibility (hemolysis percentages below 1%), platelet aggregation, cytocompatibility (cell viability above 80% in all tested cell lines), mitochondrial membrane potential (non-observed alterations) and intracellular ROS production (negligible impact compared to controls). Additionally, the nanovehicles showed acceptable cell internalization (covered area close to 100% at 30 min and 4 h) and endosomal escape abilities (significant decrease in lysosomal colocalization after 4 h of exposure). Moreover, molecular dynamics simulations were employed to better understand the underlying translocating mechanism of the OmpA protein, showing key findings regarding specific interactions with phospholipids. Overall, the versatility and the notable in vitro performance of this novel nanovehicle make it a suitable and promising drug delivery technology for the potential treatment of PD.

Unlocking cellular barriers: silica nanoparticles and fullerenol conjugated cell-penetrating agents for enhanced intracellular drug delivery.

The limited delivery of cargoes at the cellular level is a significant challenge for therapeutic strategies due to the presence of numerous biological barriers. By immobilizing the Buforin II (BUF-II) peptide and the OmpA protein on magnetite nanoparticles, a new family of cell-penetrating nanobioconjugates was developed in a previous study. We propose in this study to extend this strategy to silica nanoparticles (SNPs) and silanized fullerenol (F) as nanostructured supports for conjugating these potent cell-penetrating agents. The same molecule conjugated to distinct nanomaterials may interact with subcellular compartments differently. On the obtained nanobioconjugates (OmpA-SNPs, BUF-II-PEG12-SNPs, OmpA-F, and BUF-II-PEG12-F), physicochemical characterization was performed to evaluate their properties and confirm the conjugation of these translocating agents on the nanomaterials. The biocompatibility, toxicity, and internalization capacity of nanobioconjugates in Vero cells and THP-1 cells were evaluated in vitro. Nanobioconjugates had a high internalization capacity in these cells without affecting their viability, according to the findings. In addition, the nanobioconjugates exhibited negligible hemolytic activity and a low tendency to induce platelet aggregation. In addition, the nanobioconjugates exhibited distinct intracellular trafficking and endosomal escape behavior in these cell lines, indicating their potential for addressing the challenges of cytoplasmic drug delivery and the development of therapeutics for the treatment of lysosomal storage diseases. This study presents an innovative strategy for conjugating cell-penetrating agents using silica nanoparticles and silanized fullerenol as nanostructured supports, which has the potential to enhance the efficacy of cellular drug delivery.

Risk of violence from a current or former partner: Associated factors and classification in a nationwide study in Colombia.

Intimate partner violence (IPV) includes assaults that risk a woman's bodily integrity. Intimate partners commit IPV, people with whom the victim shares (or shared) a close personal or sexual relationship. This phenomenon has a great global and national impact. Thus, it is necessary to establish trends of the risk of physical violence to women by their current or former partner in each department of Colombia and its relationship with sociodemographic and health characteristics. This study uses an ecological approach at the departmental level, with victims of intimate partner violence treated at the National Institute of Legal Medicine and Forensic Sciences (INMLyCF). Potential factors were identified through Bayesian factor analysis and were included in the model to estimate risk. The findings show that the Casanare department had the highest risk of producing victims (SMR: 2.545). In departments where the educational level of women is at or below primary school, there is a high-risk ß = 0.343 (0.285, 0.397) of them being assaulted. For the departments in which the employment of women is in sales and services or office workers, the associated factor presents a higher risk ß = 0.361 (0.201, 0.485), as in the risk related to affiliation with the social security system ß = 0.338 (0.246, 0.498), as well as sexual and reproductive life ß = 0.143 (0.003, 0.322). The following categories were associated with physical gender violence: no education and low participation in making purchases at home ß = 0.106 (0.049, 0.199), low participation in decisions about their health, and visits to family and friends ß = 0.240 (0.170, 0.299). Therefore, public health programs should strengthen women's empowerment in household decisions and increase their educational level to reduce this incidence.

Formulation of a novel antibacterial topical treatment based on Magnetite-Buforin-II-silver nanobioconjugates.

Community acquired infections caused by Meticillin-resistant Staphylococcus aureus (MRSA) have become a growing concern due to its impact on the world public health. This microorganism is a commonly spreading pathogen associated predominantly with skin infections and connected to other more severe conditions (septic shock, and generalized infection). The lack of highly effective antibiotics and treatments to control skin infections with S. aureus has led to the search of novel therapies using alternative agents such as antimicrobial peptides (AMPs). In order to obtain a viable administration route to counteract superficial skin infections (impetigo, abscesses, furuncles, and cellulitis), a topical formulation based on Magnetite-Buforin-II-silver nanobioconjugates as active antibacterial agents was designed by their dispersion in O/W concentrated emulsions. The prepared topical characterization indicated that O/W emulsions were stable in time, the droplets size remained within the appropriate values (∼1 µm) and their rheological properties, such as pseudoplastic and shear-thinning behavior, remained unchanged for up to 3 months. Additionally, hemolysis and platelet aggregation tests were acceptable (i.e., 14.72 ± 2.62% and 8.06 ± 2.90%, respectively) in compliance with the ISO-10993 standard. Furthermore, the treatment reduced significantly (p < 0.0001) the growth of both clinical isolated MRSA and wild Type S. aureus strains as evidenced by the contact diffusion method. These results are important in the context of proposing new alternatives that allow manage effectively the threat posed by the antibiotic resistant bacterial strains, which jeopardize the lives of thousands of people every year.

Social Stigma: A Systematic Review of Cognitive Insights from Behavioral Economics (1940-2019).

There are minority and stigmatized groups who face particular challenges to their full participation in society. This study's objective was to conduct a systematic review to determine theoretical and methodological underpinnings in behavioral economics that explain how stigmatization emerges within the relationship processes and social structures of individuals. Data from 1940 to 2019 were sourced from 12 relevant electronic databases such as Scopus and Web of Science. Following PRISMA guidelines for systematic reviews, 26 studies out of 3459 met the inclusion criteria. Most of the studies applied experimental economics and were published between 2002 and 2018. Overall, the articles focus their research on the experiences of discrimination based on stereotypes and test their hypotheses through economic games. The data synthesis seems to reveal weak conceptual clarity, circular reasoning, and a hint of the problem of infinite regress. Thus, these issues open new and exciting avenues for future research to explore via an array of experimental applications.

Existen grupos minoritarios y estigmatizados que enfrentan retos particulares para lograr su completa participación en sociedad. El objetivo de este estudio fue conducir una revisión sistemática para determinar los cimientos teóricos y metodológicos en economía del comportamiento que explican cómo surge la estigmatización dentro de los procesos de relacionamiento y estructuras sociales de los individuos. Los datos abarcan el período de 1940 a 2019 y se obtuvieron de 12 bases de datos electrónicas relevantes, tales como Scopus y Web of Science. Siguiendo la guía de PRISMA para revisiones sistemáticas, 26 estudios de 3459 cumplieron con los criterios de inclusión. La mayoría de los estudios aplicó economía experimental y fueron publicados entre 2002 y 2018. En general, los artículos enfocan su investigación en experiencias de discriminación basadas en estereotipos y prueban sus hipótesis a través de juegos económicos. La síntesis de los datos parece revelar una débil claridad conceptual, razonamiento circular y un atisbo del problema de regresión infinita. Lo anterior abre nuevas y emocionantes vías de investigación futura para explorar a través de una variedad de aplicaciones experimentales.