Sub-Saharan African information potential to unveil adaptations to infectious disease.

Sub-Saharan Africa is the most promising region of the world to conduct high-throughput studies to unveil adaptations to infectious diseases due to several reasons, namely, the longest evolving time-depth in the Homo sapiens phylogenetic tree (at least two-third older than any other worldwide region); the continuous burden of infectious diseases (still number one in health/life threat); and the coexistence of populations practising diverse subsistence modes (nomadic or seminomadic hunter-gatherers and agropastoralists, and sedentary agriculturalists, small urban and megacity groups). In this review, we will present the most up-to-date results that shed light on three main hypotheses related with this adaptation. One is the hypothesis of coevolution between host and pathogen, given enough time for the establishment of this highly dynamic relationship. The second hypothesis enunciates that the agricultural transition was responsible for the increase of the infectious disease burden, due to the huge expansion of the sedentary human population and the cohabitation with domesticates as main reservoirs of pathogens. The third hypothesis states that the boosting of our immune system against pathogens by past selection may have resulted in maladaptation of the developed hygienic societies, leading to an increase of allergic, inflammatory and autoimmune disorders. Further work will enlighten the biological mechanisms behind these main adaptations, which can be insightful for translation into diagnosis, prognosis and treatment interventions.

Accuracy of different digital acquisition methods in complete arch implant-supported prostheses: An in vitro study.

STATEMENT OF PROBLEM: Digital methods such as intraoral scanners for recording the location of implants supporting complete arch prostheses have limitations. Photogrammetry devices should be able to digitize implant positions accurately, but standardized comparisons between different digital acquisition methods are lacking. PURPOSE: The purpose of this in vitro study was to compare the repeatability of different digital acquisition methods for complete arch prostheses supported by 6 and 4 implants. MATERIAL AND METHODS: A master cast was created with 6 and 4 dental implants with multiunit abutments to obtain the master digital casts. The evaluated devices were the industrial high-resolution 12-megapixel scanner (reference) Atos Compact Scan 12M (GOM), the laboratory scanners D2000 (3Shape A/S) and S900 Arti (Zirkonzahn), the photogrammetry devices iCam (iMetric4D) and PIC (PIC Dental), and the intraoral scanners TRIOS 3 (3Shape A/S) and iTero Element 5D (Align Technology). The resulting files were imported to a computer-aided design software program (exocad GmbH) to obtain the implant replicas as standard tessellation language (STL) files. These files were imported into a software program (Geomagic Control X) and superimposed per group through the best-fit algorithm to determine repeatability, defined as the closeness of agreement between each group's scanned results as root mean square (RMS) values. The normality of distribution was tested by the Shapiro-Wilk normality test, and the Kruskal-Wallis test with adjustment with the Bonferroni correction method was used accordingly (α=.05). RESULTS: The repeatability means and 95% confidence intervals for the 4 implant scans were: 1.07 µm (0.86; 1.29) for GOM, 2.05 µm (1.89; 2.21) for D2000, 3.61 µm (3.23; 3.99) for S900, 7.01 µm (6.11; 7.91) for iCam, 5.18 µm (4.6; 5.76) for PIC, 20.52 µm (18.33; 22.72) for TRIOS3, and 20.5 µm (17.37; 23.63) for iTero. Statistically significant differences were found between devices, except for iCam versus PIC, GOM versus S900, iCam versus D2000, PIC versus D2000, and TRIOS3 versus iTero. The repeatability means and 95% confidence intervals for the 6 implant groups were: 1.36 µm (1.08; 1.65) for GOM, 3.17 µm (3.01; 3.33) for D2000, 2.15 µm (2.04; 2.25) for S900, 8.67 µm (8.06; 9.28) for iCam, 13.88 µm (12.62; 15.14) for PIC, 40.32 µm (36.29; 44.36) for TRIOS3, and 38.86 µm (34.01; 43.71) for iTero. Statistically significant differences were detected between devices, except for S900 versus GOM, PIC versus iCam, and iTero versus TRIOS 3. CONCLUSIONS: The results suggest that photogrammetry could be a suitable alternative for recording implant locations of complete arch prostheses supported by 4 or 6 implants, with better repeatability than intraoral scanners. Increasing the number of implants decreased the repeatability of every device tested except the laboratory scanners.

The psychometric properties of the adolescent dissociative experiences scale (A-DES) in a sample of Portuguese at-risk adolescents.

Dissociation is a process that often occurs as a sequela of psychological trauma, and it is interrelated with psychological and behavioral problems. In the at-risk adolescent population, dissociation is often underdiagnosed and undertreated. Having reliable measures to assess this phenomenon can help in identifying adolescents at-risk and improve treatment outcomes. This study assessed the psychometric properties of the Adolescent Dissociative Experiences Scale (A-DES) with a sample of 402 Portuguese adolescents recruited from three at-risk populations. Participants completed self-report measures of trauma exposure, posttraumatic symptoms, psychological and behavioral problems, and the A-DES. A subset of the sample also completed test-retest measures. Confirmatory factor analyses revealed a best-fitting 3-factor model. Analyses revealed good internal consistencies and good agreement test-retest reliability for the scale overall and the factor-based sub-scales. Construct and predictive validity was supported with results showing that A-DES discriminates between youth reporting high versus low levels of cumulative trauma exposure and youth who meet or do not meet criteria for a probable PTSD diagnosis. Study findings replicate prior research supporting a 3-factor model of dissociation and the usefulness of A-DES to identify adolescents with dissociative symptoms. Clinical and research implications are discussed.

Alternative Models of DSM-5 Posttraumatic Stress Disorder in Portuguese Adolescents Exposed to Trauma and Childhood Adversity.

The factor structure of DSM-5 posttraumatic stress disorder (PTSD) has been extensively debated, with evidence supporting the recently proposed seven-factor hybrid model. However, few studies examining PTSD symptom structure have assessed the implications of these proposed models on diagnostic criteria and PTSD prevalence. In the present study, we examined seven alternative DSM-5 PTSD models within a confirmatory factor analysis (CFA), using the Child PTSD Symptom Scale-Self-Report for DSM-5 (CPSS-5). Additionally, we generated prevalence rates for each of the seven models by using a symptom-based diagnostic algorithm and assessed whether substance abuse, depression, anxiety symptoms, and daily functioning were differentially associated with PTSD depending on the model used to derive the diagnosis. Participants were 317 adolescents aged 13-17 years (M = 15.93, SD = 1.23) who had experienced a DSM-5 Criterion A trauma and/or childhood adversity. The CFA results showed good fit indices for all models, with the seven-factor hybrid model presenting the best fit. The rates of PTSD diagnosis varied according to each model. The four-factor DSM-5 model presented the highest rate (30.6%), and the seven-factor hybrid model presented the lowest rate (17.4%). Similar to the CFA analysis, the inclusion criteria for the diagnosis based on the hybrid model also presented the strongest associations with daily functional impairment, odds ratio (OR) = 1.48, 95% CI [1.25, 1.75]; and adverse childhood experiences, OR = 1.46, 95% CI [1.16, 1.82]. Research and clinical implications of these results are discussed, and suggestions for future investigation are presented.

NMR Metabolomics Reveals Metabolism-Mediated Protective Effects in Liver (HepG2) Cells Exposed to Subtoxic Levels of Silver Nanoparticles.

The expansion of biomedical and therapeutic applications of silver nanoparticles (AgNPs) raises the need to further understand their biological effects on human cells. In this work, NMR metabolomics has been applied to reveal the metabolic effects of AgNPs toward human hepatoma (HepG2) cells, which are relevant with respect to nanoparticle accumulation and detoxification. Cellular responses to widely disseminated citrate-coated AgNPs (Cit30) and to emergent biogenic AgNPs prepared using an aqueous plant extract as reducing and stabilizing agent (GS30) have been compared with a view to assess the influence of nanoparticle coating on the metabolic effects produced. Subtoxic concentrations (IC5 and IC20) of both nanoparticle types caused profound changes in the cellular metabolome, suggesting adaptations in energy production processes (glucose metabolism and the phosphocreatine system), antioxidant defenses, protein degradation and lipid metabolism. These signatures were proposed to reflect mainly metabolism-mediated protective mechanisms and were found to be largely common to Cit30 and GS30 AgNPs, although differences in the magnitude of response, not captured by conventional cytotoxicity assessment, were detected. Overall, this study highlights the value of NMR metabolomics for revealing subtoxic biological effects and helping to understand cell-nanomaterial interactions.

Fluorescent Bioactive Corrole Grafted-Chitosan Films.

Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15-tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices.

The Strongest Correlates of PTSD for Firefighters: Number, Recency, Frequency, or Perceived Threat of Traumatic Events?

Firefighters experience a wide range of traumatic events while on duty and are at risk to develop psychopathology and posttraumatic stress disorder (PTSD). According to cognitive models, the person's interpretation of the traumatic event is responsible for the development of PTSD rather than the traumatic event itself. This cross-sectional study aimed to explore the contribution of perceived threat to explain PTSD symptoms in Portuguese firefighters, after adjusting for potential confounding factors. A sample of 397 firefighters completed self-report measures of exposure to traumatic events, psychopathology, and PTSD. Perceived threat explained unique variance in PTSD symptoms, R(2) = .40, ΔR(2) = .02, F(10, 367) = 24.55, p < .001, Cohen's f(2) =.03, after adjusting for psychopathology, number, recency, and frequency of the events, and other potential confounding variables. The association between psychopathology and PTSD was also moderated by perceived threat, R(2) = .43, ΔR(2) = .03, F(11, 366) = 25.33, p < .001, Cohen's f(2) =.05. Firefighters may benefit from interventions that focus on perceived threat to prevent PTSD symptoms.

Psychopathology among youths who were victims of documented childhood maltreatment.

BACKGROUND: There is an established relationship between childhood maltreatment and later psychopathology, but most studies have used self-reports and only consider a small number of experiences. The main aim of this study was to examine predictors of psychopathology by comparing two sources (official records vs. self-reports) of ten different childhood adversities among youths who were identified by Child Protective Services (CPS). We also used a comparison group that was not identified by CPS. This study also compared, in terms of psychopathology, three groups of respondents (under-report; agreement; and over-report) based on the discrepancy between the two sources of childhood adversity. METHOD: The sample included 136 youths, ages 14-23 years, identified by CPS prior to age 12 as being maltreated and who lived with their family for at least 5 years. The comparison group included 80 youths. RESULTS: The identified youths were not different from the comparison group in global psychopathology. Psychopathology was associated only with the total amount of self-reported adverse experiences, with depressive symptoms being predicted by both documented and self-reported sexual abuse. Females reported and had more documented adversities, presenting an increased risk for psychopathology. The under-report group had a higher mean of documented experiences and a lower mean in psychopathology. CONCLUSIONS: Despite the limitations of a self-report methodology, our findings attest to its contribution in predicting health outcomes. Professionals from CPS need to be thorough when assessing and documenting the multiple experiences that may co-occur in a household, paying particular attention when young girls are involved, as the experience of sexual abuse has been shown to be independently associated with later risk of developing depressive symptoms. This process may increase the appropriateness of the chosen interventions.

The Role of Life Stages in the Sensitivity of Hediste diversicolor to Nanoplastics: A Case Study with Poly(Methyl)Methacrylate (PMMA).

The presence of plastic particles in oceans has been recognized as a major environmental concern. The decrease in particle size increases their ability to directly interact with biota, with particles in the nanometer size range (nanoplastics-NPs) displaying a higher ability to penetrate biological membranes, which increases with the decrease in particle size. This study aimed to evaluate the role of life stages in the effects of poly(methyl)methacrylate (PMMA) NPs on the polychaete Hediste diversicolor, a key species in the marine food web and nutrient cycle. Thus, behavioral (burrowing activity in clean and spiked sediment) and biochemical endpoints (neurotransmission, energy reserves, antioxidant defenses, and oxidative damage) were assessed in juvenile and adult organisms after 10 days of exposure to spiked sediment (between 0.5 and 128 mg PMMA NPs/Kg sediment). Overall, the results show that H. diversicolor is sensitive to the presence of PMMA NPs. In juveniles, exposed organisms took longer to burrow in sediment, with significant differences from the controls being observed at all tested concentrations when the test was performed with clean sediment, whereas in PMMA NP-spiked sediment, effects were only found at the concentrations 8, 32, and 128 mg PMMA NPs/Kg sediment. Adults displayed lower sensitivity, with differences to controls being found, for both sediment types, at 8, 32, and 128 mg PMMA NPs/Kg sediment. In terms of Acetylcholinesterase, used as a marker of effects on neurotransmission, juveniles and adults displayed opposite trends, with exposed juveniles displaying increased activity (suggesting apoptosis), whereas in adults, overall decreased activity was found. Energy-related parameters revealed a generally similar pattern (increase in exposed organisms) and higher sensitivity in juveniles (significant effects even at the lower concentrations). NPs also demonstrated the ability to increase antioxidant defenses (higher in juveniles), with oxidative damage only being found in terms of protein carbonylation (all tested NPs conditions) in juveniles. Overall, the data reveal the potential of PMMA NPs to affect behavior and induce toxic effects in H. diversicolor, with greater effects in juveniles.

Resilience in the aftermath of trauma: Classes of adjustment in at-risk youth.

OBJECTIVE: Youth who have been exposed to potentially traumatic events are at risk of developing chronic and severe adjustment problems. However, some youth exposed to potentially traumatic events exhibit better-than-expected adaptation. Person-centered analyses, based on multiple criteria for adaptive behavior and adversity, are well-suited to empirically identifying different patterns of adaptation among high-risk youth. METHOD: Data from 381 youth from three at-risk subgroups in Portugal were collected using self-reported measures of trauma history, trauma-related symptomatology, coping skills, and perceived social support. Distinct classes of adaptation after traumatic experiences were examined with latent class analysis. RESULTS: Four classes were identified: (a) trauma-related psychopathology class (13.6%), (b) adaptive resilience class (36.8%), (c) low resources class (11.4%), and (d) high resources class (38.2%). Trauma-related psychopathology class and low resources class were characterized by high levels of maladjustment. Similarly to the low resources class, the trauma-related psychopathology class reported a significantly higher likelihood of trauma-related psychopathology and higher levels of problem-solving skills. The adaptive resilience class and high resources class also reported lower levels of maladjustment, and the high resources class reported higher levels of coping skills and lower levels of externalizing problems than any other class. CONCLUSION: Clinicians treating children's internalizing mental health or externalizing behavior problems should assess trauma history and trauma-related psychopathology, as well as protective resources that may enhance resilience such as skills for problem solving and social support seeking. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimized Synthesis of Poly(Lactic Acid) Nanoparticles for the Encapsulation of Flutamide.

Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.

Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard.

Posttraumatic stress disorder symptoms and dissociation as serial mediators of the relationship between cumulative victimization and adjustment problems among poly-victimized at-risk youth.

INTRODUCTION: Poly-victimization (PV) has a greater adverse impact on adolescents' lives than any single victimization type, even when repeatedly experienced. Adolescents who experience PV tend to present with an array of adjustment problems, and research has begun to identify mechanisms linking PV to adjustment problems. Both posttraumatic stress disorder (PTSD) and dissociation are linked to PV and adjustment problems; however, it is unclear how these variables play a role in the pathways from PV to adjustment problems. This study assessed PTSD and dissociation as serial mediators in the PV-adjustment problems link. METHOD: Two hundred eighteen Portuguese youth identified as poly-victims (56% girls) and aged between 12 and 17 years old (M = 15.63; SD = 1.26) were recruited from three at-risk contexts' cohorts. Participants completed self-report measures of trauma exposure, posttraumatic symptoms, dissociative symptoms, and emotional and social adjustment problems. RESULTS: The study results suggest that, among poly-victim adolescents, PTSD and dissociation may be mediators of the relationship between the cumulative extent of victimization and adjustment problems. CONCLUSION: The current study's findings highlight the importance of careful assessment of both PTSD and dissociative symptoms and indicate that targeted interventions are essential when working with poly-victimized youth with the highest scores of cumulative victimization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Solventless Photopolymerizable Paper Coating Formulation for Packaging Applications.

Nowadays, packaging applications require the use of advanced materials as well as production methods that have a low environmental impact. In this study, a solvent-free photopolymerizable paper coating was developed using two acrylic monomers (2-ethylhexyl acrylate and isobornyl methacrylate). A copolymer, with a molar ratio of 2-ethylhexyl acrylate/isobornyl methacrylate of 0.64/0.36, was prepared and used as the main component of the coating formulations (50 and 60 wt%). A mixture of the monomers with the same proportion was used as a reactive solvent, yielding formulations with 100% solids. The coated papers showed an increase in the pick-up values from 6.7 to 32 g/m2 depending on the formulation used and the number of coating layers (up to two). The coated papers maintained their mechanical properties and presented improved air barrier properties (Gurley's air resistivity of ≈25 s for the higher pick-up values). All the formulations promoted a significant increase in the paper's water contact angle (all higher than 120 °) and a remarkable decrease in their water absorption (Cobb values decrease from 108 to 11 g/m2). The results confirm the potential of these solventless formulations for fabricating hydrophobic papers with potential application in packaging, following a quick, effective, and more sustainable approach.

The mediating role of posttraumatic stress symptoms on somatization in adolescents: A two-wave longitudinal study.

OBJECTIVE: Trauma as well as adverse childhood experiences (ACEs) have been associated with increased rates of later somatization symptoms. Some evidence has proposed that posttraumatic stress symptoms (PTSS) can mediate this relationship. However, most data come from adult samples. This two-wave longitudinal study aimed to investigate the relationship between cumulative adversity (total amount of adverse and traumatic experiences), PTSS and somatization symptoms in adolescents. METHOD: The sample included 150 adolescents, mean age of 16 years old (M = 15.99, SD = 1.25) with 67 (44.7%) males and 83 (55.3%) females. All were exposed to at least one traumatic event or one childhood adversity. The interval time between the two assessments was about 1 year. RESULTS: The results showed that the PTSS Cluster E, alterations in arousal and reactivity, partially mediated the relationship between cumulative adversity and somatization symptoms (B = .09, BSE = .03, CI [.01, .15]). However, the effect size of the mediation was medium, while the direct effect was large (B = .34, BSE = .08, CI [.18, .50]). CONCLUSIONS: While arousal and reactivity symptoms seem to play a key role in adolescents suffering from somatization symptoms, cumulative adversity have their own direct and strong contribution. Clinicians should consider assessing PTSS and cumulative adversity when caring for adolescents suffering with somatic symptoms to better deliver intervention plans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nanofibrillated cellulose/gellan gum hydrogel-based bioinks for 3D bioprinting of skin cells.

The development of suitable bioinks is an important research topic in the field of three-dimensional (3D) bioprinting. Herein, novel hydrogel-based bioinks composed of nanofibrillated cellulose (NFC) and gellan gum (GG) in different NFC/GG mass proportions (90:10, 80:20, 70:30, and 60:40) were developed and characterized. The increase in the content of GG, as well as its combination with NFC, enhanced their rheological properties, increasing both storage (G') and loss (G") moduli and the G' recovery capacity of the hydrogels (from 70.05 ± 3.06 % (90:10) to 82.63 ± 1.21 % (60:40)), as well as their mechanical properties, increasing the compressive stiffness and stress from 114.02 ± 10.93 Pa (90:10) to 337.16 ± 34.03 Pa (60:40) and from 18.27 ± 1.32 kPa (90:10) to 47.17 ± 3.59 kPa (60:40), respectively. The hydrogels were non-cytotoxic against human keratinocyte cells (HaCaT), with cell viabilities above 70 % for up to 72 h. The hydrogel 60:40 was loaded with HaCaT cells (3 × 106 cells mL-1) and bioprinted. The cell viability was maintained elevated until day 7 (90 ± 3 %) after bioprinting. These results highlight that the combination of these two biopolymers was a good strategy for the development of novel hydrogel-based bioinks for extrusion 3D bioprinting applications.

Serum amyloid A proteins reduce bone mass during mycobacterial infections.

Introduction: Osteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. Methods: Genetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussion: We found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.

Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium.

Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance. Protein nanofibrils (NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructures with excellent mechanical performance and antioxidant activity, which can work as nanotemplates to produce metallic nanoparticles. Here, gold nanoparticles (AuNPs) were synthesized in situ in the presence of LNFs, and the obtained hybrid AuNPs@LNFs were incorporated into gelatin-hyaluronic acid (HA) hydrogels for myocardial regeneration applications. The resulting nanocomposite hydrogels showed improved rheological properties, mechanical resilience, antioxidant activity, and electrical conductivity, especially for the hydrogels containing AuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogels are favorably adjusted at lower pH levels, which correspond to the ones in inflamed tissues. These improvements were observed while maintaining important properties, namely, injectability, biocompatibility, and the ability to release a model drug. Additionally, the presence of AuNPs allowed the hydrogels to be monitorable through computer tomography. This work demonstrates that LNFs and AuNPs@LNFs are excellent functional nanostructures to formulate injectable biopolymeric nanocomposite hydrogels for myocardial regeneration applications.

InfectionCMA: A Cell MicroArray Approach for Efficient Biomarker Screening in In Vitro Infection Assays.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the scientific community to acquire knowledge in real-time, when total lockdowns and the interruption of flights severely limited access to reagents as the global pandemic became established. This unique reality made researchers aware of the importance of designing efficient in vitro set-ups to evaluate infectious kinetics. Here, we propose a histology-based method to evaluate infection kinetics grounded in cell microarray (CMA) construction, immunocytochemistry and in situ hybridization techniques. We demonstrate that the chip-like organization of the InfectionCMA has several advantages, allowing side-by-side comparisons between diverse cell lines, infection time points, and biomarker expression and cytolocalization evaluation in the same slide. In addition, this methodology has the potential to be easily adapted for drug screening.

Biodistribution and pulmonary metabolic effects of silver nanoparticles in mice following acute intratracheal instillations.

The respiratory tract is the route of entry for accidentally inhaled AgNPs, which can reach the lungs and redistribute to other main organs through systemic circulation. In the present work, we aimed to evaluate silver biodistribution and biological effects after 1 or 2 intratracheal instillations (IT) of two differently sized PVP-coated AgNPs (5 and 50 nm-3 mg/kg) and ionic silver (AgNO3-1 mg/kg bw) in mice. Furthermore, nuclear magnetic resonance (NMR) metabolomics was applied to unveil pulmonary metabolic variations. Animals exposed to 5 nm AgNP (AgNP5) showed higher levels of ionic silver in organs, especially in the lung, spleen, kidney and liver, while animals exposed to 50 nm AgNP (AgNP50) showed higher levels of silver in the blood. Animals exposed to AgNP50 excreted higher amounts of silver than those exposed to AgNP5, which is consistent with higher tissue accumulation of silver in animals exposed to the latter. Lung metabolic profiling revealed several Ag-induced alterations in metabolites involved in different pathways, such as glycolysis and tricarboxylic acid (TCA) cycle, amino acid and phospholipid metabolism, and antioxidant defense. Notably, most of the metabolic changes observed after 1 IT were absent in animals subjected to 2 IT of AgNO3, or reversed for AgNPs, suggesting adaptation mechanisms to cope with the initial insult and recover homeostasis. Graphical abstract.