Frequency and Focus of in Vitro Studies of Microglia-Expressed Cytokines in Response to Viral Infection: A Systematic Review.

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.

Standardization of interstitial lung disease assessment by ultrasound: results from a Delphi process and web-reliability exercise by the OMERACT ultrasound working group.

OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.

Dense city centers support less evolutionary unique bird communities than sparser urban areas.

Urbanization alters avian communities, generally lowering the number of species and contemporaneously increasing their functional relatedness, leading to biotic homogenization. Urbanization can also negatively affect the phylogenetic diversity of species assemblages, potentially decreasing their evolutionary distinctiveness. We compare species assemblages in a gradient of building density in seventeen European cities to test whether the evolutionary distinctiveness of communities is shaped by the degree of urbanization. We found a significant decline in the evolutionary uniqueness of avian communities in highly dense urban areas, compared to low and medium-dense areas. Overall, communities from dense city centers supported one million years of evolutionary history less than communities from low-dense urban areas. Such evolutionary homogenization was due to a filtering process of the most evolutionarily unique birds. Metrics related to evolutionary uniqueness have to play a role when assessing the effects of urbanization and can be used to identify local conservation priorities.

Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice.

The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer's disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a "rejuvenation" of hippocampal antioxidant defense.

Non-biofilm-forming Staphylococcus epidermidis planktonic cell supernatant induces alterations in osteoblast biological function.

Staphylococcal biofilms significantly contribute to prosthetic joint infection (PJI). However, 40% of S. epidermidis PJI isolates do not produce biofilms, which does not explain the role of biofilms in these cases. We studied whether the supernatant from planktonic S. epidermidis alters osteoblast function. Non-biofilm-forming S. epidermidis supernatants (PJI- clinical isolate, healthy skin isolate (HS), and ATCC12228 reference strain) and biofilm-forming supernatants (PJI+ clinical isolate, ATCC35984 reference strain, and Staphylococcus aureus USA300 reference strain) were included. Osteoblasts stimulated with supernatants from non-biofilm-forming isolates for 3, 7, and 14 days showed significantly reduced cellular DNA content compared with unstimulated osteoblasts, and apoptosis was induced in these osteoblasts. Similar results were obtained for biofilm-forming isolates, but with a greater reduction in DNA content and higher apoptosis. Alkaline phosphatase activity and mineralization were significantly reduced in osteoblasts treated with supernatants from non-biofilm-forming isolates compared to the control at the same time points. However, the supernatants from biofilm-forming isolates had a greater effect than those from non-biofilm-forming isolates. A significant decrease in the expression of ATF4, RUNX2, ALP, SPARC, and BGLAP, and a significant increase in RANK-L expression were observed in osteoblasts treated with both supernatants. These results demonstrate that the supernatants of the S. epidermidis isolate from the PJI- and HS (commensal) with a non-biofilm-forming phenotype alter the function of osteoblasts (apoptosis induction, failure of cell differentiation, activation of osteoblasts, and induction of bone resorption), similar to biofilm-forming isolates (PJI+, ATCC35984, and S. aureus USA300), suggesting that biofilm status contributes to impaired osteoblast function and that the planktonic state can do so independently of biofilm production.

Usefulness of Lung Ultrasound as a Method for Early Diagnosis of Interstitial Lung Disease in Patients with Rheumatoid Arthritis.

Purpose: To determine the value of lung ultrasound (LUS) compared to high-resolution computed tomography (HRCT) in the early diagnosis of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Patients and Methods: An observational prospective study was performed. Were included patients with respiratory symptoms or/and, patients with crackles in auscultation during medical consultation. All patients underwent to chest X-rays, LUS, HRCT,and respiratory function tests. Results: A total of 192 patients with RA were included. Mean disease duration was 16.8 ± 11.1 years. 72% were positive for rheumatoid factor or anti-citrullinated antibodies. Of the total number of subjects, 54.7% had respiratory symptoms. The other patients did not have respiratory symptoms, but they did have had crackles on pulmonary auscultation. B lines > 11.5 on the ROC curve predicted ILD (AUC 0.63; CI 95%: 0.55-0.71; p < 0.003). A DLCO value of <7.13 significantly predicted the presence of ILD (AUC 0.61; 95% CI: 0.52-0.70; p < 0.028). Conclusion: The findings of this study suggest that LUS is a valuable tool for the early diagnosis of ILD in patients with RA, and together with DLCO, can adequately predict the presence of ILD in this population. LUS also helps to determine which patients with respiratory symptoms and signs suggestive for ILD are undergo to HRCT.

Outcomes of ECMO support with polypropylene membrane during pandemic times: a retrospective cohort study.

BACKGROUND: The SARS-CoV-2 pandemic resulted in shortages of supplies, which limited the use of extracorporeal membrane oxygenation (ECMO) support. As a contingency strategy, polypropylene (PP) oxygenation membranes were used. This study describes the clinical outcomes in patients on ECMO with PP compared to poly-methylpentene (PMP) oxygenation membranes. METHODS: Retrospective cohort of patients in ECMO support admitted between 2020 and 2021. RESULTS: A total of 152 patients with ECMO support were included, 71.05% were men with an average age of 42 (SD 9.91) years. Veno-venous configuration was performed in 75.6% of cases. The PP oxygenation membranes required more changes 22 (63.1%), than the PMP Sorin® 24 (32,8%) and Euroset® 15 (31,9%) (p.0.022). The main indication for membrane change was low oxygen transfer for PP at 56.2%, Sorin® at 50%, and Euroset® at 14.8%. Renal replacement therapy was the most frequent complication with PP membrane in 22 patients (68.7%) Sorin® 25 patients (34.2%), and Euroset® 15 patients (31.9%) (p 0.001) without statistically significant differences in mortality. CONCLUSION: PP oxygenation membranes was a useful and feasible strategy. It allowed a greater disponibility of ECMO support for critically ill in a situation of great adversity during the SARS-CoV-2 pandemic.

Evidence for alterations in lipid profiles and biophysical properties of lipid rafts from spinal cord in sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease affecting motor neurons in the spinal cord and brainstem whose etiopathogenesis remains unclear. Recent studies have linked major neurodegenerative diseases with altered function of multimolecular lipid-protein complexes named lipid rafts. In the present study, we have isolated lipid rafts from the anterior horn of the spinal cords of controls and ALS individuals and analysed their lipid composition. We found that ALS affects levels of different fatty acids, lipid classes and related ratios and indexes. The most significant changes affected the contents of n-9/n-7 monounsaturated fatty acids and arachidonic acid, the main n-6 long-chain polyunsaturated fatty acid (LCPUFA), which were higher in ALS lipid rafts. Paralleling these findings, ALS lipid rafts lower saturates-to-unsaturates ratio compared to controls. Further, levels of cholesteryl ester (SE) and anionic-to-zwitterionic phospholipids ratio were augmented in ALS lipid rafts, while sulfatide contents were reduced. Further, regression analyses revealed augmented SE esterification to (mono)unsaturated fatty acids in ALS, but to saturates in controls. Overall, these changes indicate that lipid rafts from ALS spinal cord undergo destabilization of the lipid structure, which might impact their biophysical properties, likely leading to more fluid membranes. Indeed, estimations of membrane microviscosity confirmed less viscous membranes in ALS, as well as more mobile yet smaller lipid rafts compared to surrounding membranes. Overall, these results demonstrate that the changes in ALS lipid rafts are unrelated to oxidative stress, but to anomalies in lipid metabolism and/or lipid raft membrane biogenesis in motor neurons. KEY MESSAGES: The lipid matrix of multimolecular membrane complexes named lipid rafts are altered in human spinal cord in sporadic amyotrophic lateral sclerosis (ALS). Lipid rafts from ALS spinal cord contain higher levels of n-6 LCPUFA (but not n-3 LCPUFA), n-7/n-9 monounsaturates and lower saturates-to-unsaturates ratio. ALS lipid rafts display increased contents of cholesteryl esters, anomalous anionic-to-zwitterionic phospholipids and phospholipid remodelling and reduced sulphated and total sphingolipid levels, compared to control lipid rafts. Destabilization of the lipid structure of lipid raft affects their biophysical properties and leads to more fluid, less viscous membrane microdomains. The changes in ALS lipid rafts are unlikely related to increased oxidative stress, but to anomalies in lipid metabolism and/or raft membrane biogenesis in motor neurons.

Hydrolyzed sewage sludge as raw bio-based material for hermetic bag production.

This study aimed to assess the potential of sewage sludge, a significant residue of wastewater treatment plants (WWTPs), as a sustainable resource for producing a bio-based material for hermetic bags (BMHB), in order to reduce the dependency on petroleum-derived plastics. The approach involved the application of thermal hydrolysis to solubilize sewage sludge, and it systematically examined critical process parameters, including temperature (120-150 °C), residence time (1-4 h), and medium pH (6.6-10). Results revealed that alkaline thermal hydrolysis significantly enhanced biomolecule solubilization, particularly proteins (289 ± 1 mg/gVSSo), followed by humic-like substances (144 ± 6 mg/gVSSo) and carbohydrates (49 ± 2 mg/gVSSo). This condition also increased the presence of large-and medium-sized compounds, thereby enhancing BMHB mechanical resistance, with puncture resistance values reaching 63.7 ± 0.2 N/mm. Effective retention of UV light within the 280-400 nm range was also observed. All BMHB samples exhibited similar properties, including water vapor permeability (WVP) (∼3.9 g * mm/m2 * h * kPa), hydrophilicity (contact angles varied from 35.4° ± 0.3 to 64° ± 5), solubility (∼95%), and thermal stability (∼74% degradation at 700 °C). Notably, BMHB proved to be an eco-friendly packaging for acetamiprid, an agricultural pesticide, preventing direct human exposure to harmful substances. Testing indicated rapid pesticide release within 5 min of BMHB immersion in water, with only 5% of BMHB residues remaining after 20 min. Additionally, the application of this material in soil was considered safe, as it met regulatory limits for heavy metal content and exhibited an absence of microorganisms.

Antioxidant Activity of Egg Yolk Protein Hydrolysates Obtained by Enzymatic and Sub-Critical Water Hydrolysis.

Obtaining peptides with antioxidant properties by enzymatic hydrolysis has been widely described; however, the use of non-enzymatic methods to obtain peptides with antioxidant capacities has been poorly investigated. In this study, non-soluble proteins obtained from delipidated egg yolk granules were hydrolyzed with trypsin, and with a non-enzymatic method using sub-critical water hydrolysis under a non-oxidizing (nitrogen) and oxidizing (oxygen) atmosphere. The effect of the sub-critical water hydrolysis on the amino acids' composition of the hydrolysates was assessed. Furthermore, the antioxidant capacities of the hydrolysates were evaluated using the ABTS•+ scavenging assay, the DPPH radical scavenging activity assay, and by measuring the reducing power of the peptides, the peptides' ferrous ion chelating capacities, and the antioxidant effect of the peptides on beef homogenates. The hydrolysate obtained by sub-critical water hydrolysis under a nitrogen stream showed similar or better results in the antioxidant tests than those obtained using trypsin hydrolysis, except in the ferrous chelating capacity, where the trypsin hydrolysate showed the best performance. The oxidizing environment promoted by the oxygen in the other sub-critical water hydrolysis method tested produced the peptides with the lowest antioxidant capacities, due to changes in the primary structure of the peptides. These results suggest that the sub-critical water hydrolysis method under a nitrogen stream, in comparison with the enzymatic hydrolysis, is a reliable method to obtain peptides with good antioxidant capacities.

Nucleotides as Bacterial Second Messengers.

In addition to comprising monomers of nucleic acids, nucleotides have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells. The most common example is cyclic AMP (cAMP). Nucleotide signaling is a focus of great interest in bacteria. Cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, and virulence. Moreover, the cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells to allow for infection. On the other hand, non-cyclic nucleotide molecules pppGpp and ppGpp are alarmones involved in regulating the bacterial response to nutritional stress; they are also considered second messengers. These second messengers can potentially be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, the role of c-di-nucleotides and cAMP as second messengers in different bacterial processes is addressed.

Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver.

Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH. However, testosterone exerts many effects on liver through complex and poorly understood mechanisms. Testosterone impacts liver functions by binding to the Androgen Receptor, and, indirectly, through its conversion to estradiol, and cooperation with GH. However, the role of testosterone, and its interaction with GH, in the hypothyroid liver, remains unclear. In the present work, the effects of testosterone, and how they impact on GH-regulated whole transcriptome and lipid composition in the liver, were studied in the context of adult hypothyroid-orchiectomized rats. Testosterone replacement positively modulated somatotropic-liver axis and impacted liver transcriptome involved in lipid and glucose metabolism. In addition, testosterone enhanced the effects of GH on the transcriptome linked to lipid biosynthesis, oxidation-reduction, and metabolism of unsaturated and long-chain fatty acids (FA). However, testosterone decreased the hepatic content of cholesterol esters and triacylglycerols and increased fatty acids whereas GH increased neutral lipids and decreased polar lipids. Biological network analysis of the effects of testosterone on GH-regulated transcriptome confirmed a close connection with crucial proteins involved in steroid and fatty acid metabolism. Taken together, this comprehensive analysis of gene expression and lipid profiling in hypothyroid male liver reveals a functional interplay between testosterone and pulsed GH administration.

Chondrogenic Potential of Human Adipose-Derived Mesenchymal Stromal Cells in Steam Sterilized Gelatin/Chitosan/Polyvinyl Alcohol Hydrogels.

Cross-linked polymer blends from natural compounds, namely gelatin (Gel), chitosan (CS), and synthetic poly (vinyl alcohol) (PVA), have received increasing scrutiny because of their versatility, biocompatibility, and ease of use for tissue engineering. Previously, Gel/CS/PVA [1:1:1] hydrogel produced via the freeze-drying process presented enhanced mechanical properties. This study aimed to investigate the biocompatibility and chondrogenic potential of a steam-sterilized Gel/CS/PVA hydrogel using differentiation of human adipose-derived mesenchymal stromal cells (AD-hMSC) and cartilage marker expression. AD-hMSC displayed fibroblast-like morphology, 90% viability, and 69% proliferative potential. Mesenchymal profiles CD73 (98.3%), CD90 (98.6%), CD105 (97.0%), CD34 (1.11%), CD45 (0.27%), HLA-DR (0.24%); as well as multilineage potential, were confirmed. Chondrogenic differentiation of AD-hMSC in monolayer revealed the formation of cartilaginous nodules composed of glycosaminoglycans after 21 days. Compared to nonstimulated cells, hMSC-derived chondrocytes shifted the expression of CD49a from 2.82% to 40.6%, CD49e from 51.4% to 92.2%, CD54 from 9.66 to 37.2%, and CD151 from 45.1% to 75.8%. When cultured onto Gel/CS/PVA hydrogel during chondrogenic stimulation, AD-hMSC changed to polygonal morphology, and chondrogenic nodules increased by day 15, six days earlier than monolayer-differentiated cells. SEM analysis showed that hMSC-derived chondrocytes adhered to the surface with extended filopodia and abundant ECM formation. Chondrogenic nodules were positive for aggrecan and type II collagen, two of the most abundant components in cartilage. This study supports the biocompatibility of AD-hMSC onto steam-sterilized GE/CS/PVA hydrogels and its improved potential for chondrocyte differentiation. Hydrogel properties were not altered after steam sterilization, which is relevant for biosafety and biomedical purposes.

Absceso del psoas secundario a apendicitis atípica en gestante. Presentación de un caso

El absceso del psoas es una enfermedad infecciosa infrecuente y de difícil diagnóstico, caracterizado por una colección purulenta a nivel de este músculo, que provoca un síndrome de respuesta inflamatoria sistémica. La infección puede ser primaria por diseminación hematógena, o secundaria, a partir de un foco infeccioso cercano. Su presentación durante el embarazo es rara, y predomina la forma primaria, razón por la cual se decidió realizar este artículo. Se presenta el caso de una gestante con 28,4 semanas de edad gestacional que ingresó por dolor inguinal con posterior irradiación a la cadera, flanco y región lumbar derechos; postura en flexión de la cadera derecha y marcha antiálgica, así como aparición, a los nueve días de iniciados los síntomas, de una masa dolorosa entre fosa ilíaca y flanco derechos. Los hallazgos de la ecografía abdominal y la resonancia permitieron el diagnóstico de un plastrón apendicular con un apéndice retrocecal, así como absceso del psoas derecho, los cuales se trataron con antibioticoterapia y drenaje percutáneo del absceso, con resultados satisfactorios. El absceso del psoas secundario puede constituir el debut de una apendicitis atípica retrocecal, y para su diagnóstico hay que tener un alto nivel de sospecha por su clínica inespecífica.

The psoas abscess is a rare infectious disease that is difficult to diagnose, characterized by a purulent collection at the level of this muscle, which causes a systemic inflammatory response syndrome. The infection can be primary by hematogenous dissemination, or secondary, from a nearby infectious focus. Its presentation during pregnancy is rare, and the primary form predominates, which is why it was decided to write this article. The case of a pregnant woman with a gestational age of 28.4 weeks who was admitted due to inguinal pain with subsequent irradiation to the right hip, flank, and lumbar region; flexed posture of the right hip and analgesic gait, as well as the appearance, nine days after the onset of symptoms, of a painful mass between the right iliac fossa and flank it is presented. The findings of the abdominal ultrasound and MRI allowed the diagnosis of an appendiceal plastron with a retrocecal appendix, as well as a right psoas abscess, which were treated with antibiotic therapy and percutaneous drainage of the abscess, with satisfactory results. Secondary psoas abscess may constitute the debut of atypical retrocecal appendicitis, and its diagnosis requires a high level of suspicion due to its non-specific symptoms.

Effect of Birch Sap as Solvent and Source of Bioactive Compounds in Casein and Gelatine Films.

Birch sap consists of a natural water-based solution with valuable compounds such as minerals, sugars, organic acids and phenolic compounds that can be used advantageously in the preparation of edible films. In this study, gelatine- and casein-based films were prepared using birch sap as biopolymer solvent and source of bioactive compounds with the aim of developing new bioactive materials for food packaging. The physical, mechanical, barrier, antioxidant and iron-chelating properties of the obtained films were investigated. Birch sap enhanced the mechanical properties of the films by increasing puncture strength and flexibility, as well as their ultraviolet-visible light barrier properties. In addition, the presence of bioactive compounds endowed the birch sap films with an antioxidant capacity of almost 90% and an iron-chelating capacity of 40-50% with respect to the control films. Finally, to test these films as food packaging material, a photosensitive curcumin solution was packed and exposed to ultraviolet light. Tested films were able to protect curcumin against photodegradation, and the presence of bioactive compounds inside the birch-sap-enriched materials offered an additional 10% photoprotective effect compared to control films. Results showed the potential of birch sap as an environmentally friendly biopolymer solvent and plasticizer that can improve the mechanical and photoprotective properties of the prepared materials.

Radiosterilized Pig Skin, Silver Nanoparticles and Skin Cells as an Integral Dressing Treatment for Burns: Development, Pre-Clinical and Clinical Pilot Study.

Radiosterilized pig skin (RPS) has been used as a dressing for burns since the 1980s. Its similarity to human skin in terms of the extracellular matrix (ECM) allows the attachment of mesenchymal stem cells, making it ideal as a scaffold to create cellularized constructs. The use of silver nanoparticles (AgNPs) has been proven to be an appropriate alternative to the use of antibiotics and a potential solution against multidrug-resistant bacteria. RPS can be impregnated with AgNPs to develop nanomaterials capable of preventing wound infections. The main goal of this study was to assess the use of RPS as a scaffold for autologous fibroblasts (Fb), keratinocytes (Kc), and mesenchymal stem cells (MSC) in the treatment of second-degree burns (SDB). Additionally, independent RPS samples were impregnated with AgNPs to enhance their properties and further develop an antibacterial dressing that was initially tested using a burn mouse model. This protocol was approved by the Research and Ethics Committee of the INRLGII (INR 20/19 AC). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis of the synthesized AgNPs showed an average size of 10 nm and rounded morphology. Minimum inhibitory concentrations (MIC) and Kirby-Bauer assays indicated that AgNPs (in solution at a concentration of 125 ppm) exhibit antimicrobial activity against the planktonic form of S. aureus isolated from burned patients; moreover, a log reduction of 1.74 ± 0.24 was achieved against biofilm formation. The nanomaterial developed with RPS impregnated with AgNPs solution at 125 ppm (RPS-AgNPs125) facilitated wound healing in a burn mouse model and enhanced extracellular matrix (ECM) deposition, as analyzed by Masson's staining in histological samples. No silver was detected by energy-dispersive X-ray spectroscopy (EDS) in the skin, and neither by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in different organs of the mouse burn model. Calcein/ethidium homodimer (EthD-1), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and scanning electron microscopy (SEM) analysis demonstrated that Fb, Kc, and MSC could attach to RPS with over 95% cell viability. Kc were capable of releasing FGF at 0.5 pg above control levels, as analyzed by ELISA assays. An autologous RPS-Fb-Kc construct was implanted in a patient with SDB and compared to an autologous skin graft. The patient recovery was assessed seven days post-implantation, and the patient was followed up at one, two, and three months after the implantation, exhibiting favorable recovery compared to the gold standard, as measured by the cutometer. In conclusion, RPS effectively can be used as a scaffold for the culture of Fb, Kc, and MSC, facilitating the development of a cellularized construct that enhances wound healing in burn patients.

Continuous precipitation-filtration process for initial capture of a monoclonal antibody product using a four-stage countercurrent hollow fiber membrane washing step.

The significant increase in product titers, coupled with the growing focus on continuous bioprocessing, has renewed interest in using precipitation as a low-cost alternative to Protein A chromatography for the primary capture of monoclonal antibody (mAb) products. In this work, a commercially relevant mAb was purified from clarified cell culture fluid using a tubular flow precipitation reactor with dewatering and washing provided by tangential flow microfiltration. The particle morphology was evaluated using an inline high-resolution optical probe, providing quantitative data on the particle size distribution throughout the precipitation process. Data were obtained in both a lab-built 2-stage countercurrent washing system and a commercial countercurrent contacting skid that provided 4 stages of continuous washing. The processes were operated continuously for 2 h with overall mAb yield of 92 ± 3% and DNA removal of nearly 3 logs in the 4-stage system. The high DNA clearance was achieved by selective redissolution of the mAb using a low pH acetate buffer. Host cell protein clearance was 0.59 ± 0.08 logs, comparable to that based on model predictions. The process mass intensity was slightly better than typical Protein A processes and could be significantly improved by preconcentration of the antibody feed material.

Valorisation of the residual aqueous phase from hydrothermally liquefied black liquor by persulphate-based advanced oxidation.

Hydrothermal liquefaction of Kraft black liquor is a promising method for the production of valuable organic chemicals. However, the separation of the biochar and biocrude leaves a residual aqueous phase in large volumes, which needs to be properly managed to make the process profitable. In this work, the persulphate-based advanced oxidation was assessed, for the first time ever, as a pretreatment of this aqueous phase to reduce its content of phenolic compounds and alcohols, which hinder further valorisation strategies. Results revealed that the phenolic compounds and the alcohols were oxidised in presence of low persulphate anion concentrations (<50 mM), mainly to quinone-like compounds and organic acids. At higher oxidant concentrations, these intermediates were subsequently oxidised to valuable acetic acid. When Fe (II) was added as the catalyst, low concentrations (<9 mM) enhanced the degradation of both phenolic compounds and alcohols due to the increase of the sulphate radicals, consequently reducing persulphate requirements for their removal. Nevertheless, higher Fe (II) doses produced the sequestration of sulphate radicals, thus decreasing the oxidation performance and generating undesired parallel reactions.

[Chemotherapy at the end of life is compatible with dignified death and palliative care] / Quimioterapia al final de la vida es compatible con muerte digna y cuidados paliativos.

Introduction: Cancer treatment is increasingly aggressive. The aim was to estimate who died due to cancer, to report use of chemotherapy (CT) in the last 3 months of life, and to describe clinical-epidemiological characteristics of these patients. Methods: We included a consecutive sample of deceased during 2017, affiliated to Hospital Italiano de Buenos Aires. Through manual review of medical helath records, they were classified according to the cause of death (cancer or other cause), validating diagnosis and baseline stage, performance status (PS). Prevalences with 95% CI are reported and descriptive statistics were used. Results: A total of 2293 adults died, 59% women with a median age of 84 years old. There were a total of 736 deaths from cancer, representing 32% (95%CI 30-34). This last subgroup were 54% women, with a median age of 75 years, and only one patient had advance directives. Regarding the place of death, 80% were hospitalized (65% general ward and 15% intensive care units). The most frequent tumors were: lung, colorectal-gastric, hematological, and breast. A total of 390 patients received CT at the end of life (53%; 95%CI 49-57), 53% being women and with a mean age of 68 years. Regarding the underlying oncological disease: 81% had a solid tumor, 75% advanced stage, and mostly with poor/regular ability to perform daily activities (25% PS3 and 32% PS4, respectively). Conclusion: There is a high frequency of CT at the end of life and deaths continue to be mainly in-hospital.

Introducción: El tratamiento oncológico es cada vez más agresivo. El objetivo de este trabajo fue estimar las personas fallecidas por causa oncológica, reportar la frecuencia de uso de quimioterapia (QT) en los últimos 3 meses de vida, y describir las características clínicas-epidemiológicas de estos pacientes. Métodos: Se incluyó una muestra consecutiva de fallecidos durante el 2017, afiliados a prepaga del Hospital Italiano de Buenos Aires. Mediante revisión de historias clínicas, se los clasificó según la causa de muerte (oncológico u otra causa), validando diagnóstico y estadio de base, performance status (PS). Se reportan prevalencias con IC95% y se utilizó estadística descriptiva. Resultados: Fallecieron 2293 personas, 59% mujeres con mediana de 84 años. Hubo un total de 736 fallecidos por cáncer, representando el 32% (IC95% 30-34). Este último subgrupo presentó una mediana de 75 años, 54% eran mujeres y sólo una paciente tenía directivas anticipadas. En cuanto al lugar de fallecimiento, 80% ocurrió hospitalizado (65% sala general y 15% unidad cerrada). Los tumores más frecuentes fueron: pulmón, colorrectal-gástrico, hematológico, y mama. Un total de 390 pacientes recibieron QT al final de la vida (53%; IC95% 49-57), siendo 53% mujeres y con promedio de 68 años. En cuanto a la enfermedad oncológica de base: 81% tenían tumor sólido, 75% estadío avanzado, y mayoritariamente con mala/regular capacidad para realizar actividades cotidianas (25% PS3 y 32% PS4 respectivamente). Conclusión: Existe una frecuencia preocupante del uso de QT en el fin de vida y los fallecimientos siguen siendo principalmente intrahospitalarios.

A standard analytical approach and establishing criteria for microplastic concentrations in wastewater, drinking water and tap water.

The ubiquitous presence of microplastics (MPs) in natural water bodies reflects the global issue regarding these micropollutants. The main problem of MPs lies on the difficulty of removing these particles from water during wastewater and drinking water treatments. The release of MPs to the environment in treated wastewater contributed to the dispersion of these micropollutants, which enhances the harmful effect of MPs on fauna and flora. In addition, their presence in tap water entails a potential risk to human health since MPs can be directly consumed. The first step is being able to quantify and characterise these microparticles accurately. In this work, a comprehensive analysis on the presence of MPs in wastewater, drinking water and tap water has been conducted with emphasis on sampling methods, pre-treatment, MP size and analytical methods. Based on literature data, a standard experimental procedure has been proposed with the objective of recommending a methodology that allows the homogenisation of MP analysis in water samples. Finally, reported MP concentrations for influents and effluents of drinking and wastewater treatment plants and tap water have been analysed, in terms of abundance, ranges and average values, and a tentative classification of different waters based on their MP concentrations is proposed.