Suitability of Hair Testing in Medical Dispensing Errors: A Fatal Case of Gliclazide Poisoning.

A patient was prescribed a new treatment, 40 mg furosemide. Her pharmacist mistakenly dispensed 40 mg gliclazide instead. After 3 weeks of treatment, the patient was found in a coma, was hospitalised and died after a week. Hair sample was collected during post-mortem examination and tested for gliclazide on three 2 cm sections, starting at the root end. Hair strands were decontaminated, segmented and incubated in the presence of diazepam-d5, and a solid-liquid extraction has been performed. Finally, toxicological analyses were performed by UFLC Shimadzu Prominence - MS/MS Sciex 6500 QTRAP. Gliclazide was found on the proximal (238 pg/mg), median (77 pg/mg) and distal (69 pg/mg) segments. The concentration in the proximal segment was largely higher than in the other two, which demonstrates repeated intake of gliclazide by the patient during at least the last 2 months before death. The lower concentrations in the medial and distal segments, as well as a part of the concentration in the proximal segment, may be linked to external hair contamination. These could be due to either radial sweat diffusion, possibly occurring in the last week hospitalisation of the patient, or to biological fluids contamination during post-mortem examination. This case illustrates the opportunity to confirm slow and fatal chronic poisoning by gliclazide using hair analysis and shows the benefit of hair testing for the investigation of medical or dispensing errors.

Cosmology and fundamental physics with the ELT-ANDES spectrograph.

State-of-the-art 19th century spectroscopy led to the discovery of quantum mechanics, and 20th century spectroscopy led to the confirmation of quantum electrodynamics. State-of-the-art 21st century astrophysical spectrographs, especially ANDES at ESO's ELT, have another opportunity to play a key role in the search for, and characterization of, the new physics which is known to be out there, waiting to be discovered. We rely on detailed simulations and forecast techniques to discuss four important examples of this point: big bang nucleosynthesis, the evolution of the cosmic microwave background temperature, tests of the universality of physical laws, and a real-time model-independent mapping of the expansion history of the universe (also known as the redshift drift). The last two are among the flagship science drivers for the ELT. We also highlight what is required for the ESO community to be able to play a meaningful role in 2030s fundamental cosmology and show that, even if ANDES only provides null results, such 'minimum guaranteed science' will be in the form of constraints on key cosmological paradigms: these are independent from, and can be competitive with, those obtained from traditional cosmological probes.

Emulsions vs excipient emulsions as α-tocopherol delivery systems: Formulation optimization and behaviour under in vitro digestion.

Oil-in-water emulsions (EM) have been extensively used for the encapsulation of lipophilic bioactive compounds and posterior incorporation into food matrices to obtain functional foods. Conversely, novel excipient oil-in-water emulsions (EXC) present identical composition and structure as EM, albeit are not bioactive by themselves since no bioactive compound is encapsulated. Instead, EXC aims at improving the bioavailability of foods' natural bioactive compounds upon co-ingestion with nutrient-rich foods. In this work, EM and EXC were produced and their stability and functionality as delivery systems for α-tocopherol compared. Emulsions were formulated with corn oil and lecithin, and their composition was optimized using experimental designs. Formulations produced with 3 % lecithin and 5 % oil attained smallest particles sizes with the lowest polydispersity index of all tested formulations and remained stable up to 60 days. Encapsulation of α-tocopherol did not have a significative impact on the structural properties of the particles produced with the same composition. α-tocopherol stability during in vitro digestion was superior in EM regardless the processing methodology (EM stability < 50 %, EXC stability < 29 %), indicating that EM offered greater protection against the digestive environment. α-tocopherol's bioaccessibility was significantly increased when encapsulated or when digested with added excipient emulsions (82-92 % and 87-90 % for EM and EXC, respectively). In conclusion, EM were more efficient vehicles for the selected bioactive compound, however, the good results obtained with EXC imply that excipient emulsions have a great potential for applications on foods to improve their natural bioactive compounds' bioavailability without the need of further processing.

Ternary composites of poly(vinylidene fluoride-co-hexafluoropropylene) with silver nanowires and titanium dioxide nanoparticles as separator membranes for lithium-ion batteries.

In the realm of polymer composites, there is growing interest in the use of more than one filler for achieving multifunctional properties. In this work, a composite separator membrane has been developed for lithium-ion battery application, by incorporating conductive silver nanowires (AgNWs) and titanium dioxide (TiO2) nanoparticles into a poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) polymer matrix. The composite membranes were manufactured by solvent casting and thermally induced phase separation, with total filler content varying up to 10 wt%. The ternary composites composites present improved mechanical characteristics, ionic conductivity and lithium transfer number compared to the neat polymer matrix. On the other hand, the filler type and content within the composite has little bearing on the morphology, polymer phase, or thermal stability. Once applied as a separator in lithium-ion batteries, the highest discharge capacity value was obtained for the 5 wt% AgNWs/5 wt% TiO2/PVDF-HFP membrane at different C-rates, benefiting from the synergetic effect from both fillers. This work demonstrates that higher battery performance can be achieved for next-generation lithium-ion batteries by using separator membranes based on ternary composites.

The effect of urbanization on species composition and trophic guilds of bats (Mammalia, Chiroptera) in the Brazilian Savanna.

Urban environments present less environmental heterogeneity in relation to the natural ones, affecting the biodiversity of bats and the ecological processes in which they participate. In this way, we will identify how urbanization influences the structure of bat communities in the municipality of Goiânia, Goiás, Brazil. We compared species composition, guilds and bat richness in a gradient that crossed urban, semi-urban and natural areas in the municipality of Goiânia, contained in the Cerrado biome. We captured a total of 775 bats of 16 species distributed in three families. Urban areas had a higher species abundance, while semi-urban areas had a higher species richness. The three types of environments have different compositions, the urban one being more homogeneous, the fauna in these areas is composed of generalist species, which benefit from this process. The diversity present in semi-urban areas is a consequence of the intersection between urban and natural fauna, which is why urban expansion needs to occur in a planned manner to minimize the impacts of this process and ensure the maintenance of biodiversity.

Dynamics of CD44+ bovine nucleus pulposus cells with inflammation.

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors. CD44 widespread expression in NP was partially associated with CD14 and CD45, resulting in the identification of distinct cell subsets. In conclusion, this study points out CD44 and CD44-based cell subsets as relevant targets in the modulation of the IVD pro-inflammatory/degenerative cascade.

Prevalence and factors associated with dry socket following routine dental extractions.

BACKGROUND: Dry socket (DS) or fibrinolytic osteitis is a relatively common complication that can occur following tooth extraction. This study aimed to determine the prevalence of DS and identify its associated predictive and mediating variables. MATERIAL AND METHODS: This study is classified as prospective observational, cross-sectional, and multicenter. Patients were consecutively selected in accordance with established criteria for tooth extraction. Data on patient demographics, surgical procedures and postoperative outcomes were collected. Nominal variables were analyzed using the Chi-Square Test, while associations involving ordinal values or considering counts or layers were examined using the Kendall's Tau-B Test or Mantel-Haenszel Test for trend. The GLM Mediation Model was employed to investigate potential mediation or indirect effects or potential underlying mechanisms of predictive variables on the development of DS. Two-tailed significance level of p ≤0.05 was considered statistically significant. RESULTS: A total of 1,357 patients undergoing routine dental extractions were included. DS was observed in 13 patients (prevalence of 1%). DS was associated with younger patients (under 50 years old), longer procedures, and the presence of surgical accidents, but only when mediated by surgical complexity. Smoking, particularly in combination with complex surgeries and surgical accidents, was associated with DS. Postoperative pain for more than two days and reported at moderate to high levels, emerged as a potential warning sign for DS. The use of antibiotics was found to significantly reduce the risk of DS (RR reduction of 36% and absolute risk reduction of 0.63%). CONCLUSIONS: Routine dental extractions revealed a 1% prevalence of dry socket. The obtained results suggests that DS is a multifactorial condition influenced by various factors, including gender, age, smoking, antibiotic prescription and surgical factors such as length, technique and accidents, nevertheless, those associations were observed mainly considering the influence of one variable on another.

Identification of APOB variants in samples from the brazilian population with hypercholesterolemic phenotype

BACKGROUND AND AIMS: Apolipoprotein B plays a crucial role in regulating plasma cholesterol by mediating the interaction of low-density lipoprotein (LDL) with LDL receptors in the liver. Inherited mutations in this gene may increase the risk of developing premature atherosclerotic cardiovascular disease, especially in individuals with familial hypercholesterolemia type 2 (FH2). The aim of this study is to identify APOB variants that may indicate pathogenicity in a sample of the Brazilian population using a data bank exome sequencing study by NGS in a Brazilian population phenotypically diagnosed by clinical and laboratory profile. This finding is going to improve genetic hypercholesteremia diagnosis. METHODS: High-quality DNA samples (n»300) were sequenced using an exon-targeted gene sequencing (ETGS) strategy to identify variants in FHrelated genes. Pathogenicity classification was based on criteria established by the American College of Medical Genetics and Genomics (ACMG), also using information from ClinVar and pathogenicity scores from previous association studies. RESULTS: A total of 121 variants were identified in APOB, of which four are novel variants missense (p.Thr626Asn, p.Ile2750Thr, p.Gln2078Lys and p.Met4184Arg). After curating pathogenicity scores, variants were classified according to the ACMG criteria. Among them four as pathogenic or likely pathogenic (p.Pro2739Leu, p.His1923Arg, p.Pro994Leu and p.Pro877Leu), and 21 variants had uncertain significance. Additionally, 92 previously known variants with uncertain significance were classified as benign or likely benign. The results were submitted to Clinvar for actualization of pathogenicity. CONCLUSIONS: These results improve the molecular diagnosis associating APOB variants with the clinical phenotype of hypercholesterolemia.

Biocellulose patch technique for fetoscopic repair of open spina bifida in twin pregnancy.

OBJECTIVES: Twin pregnancy is currently an exclusion criterion for prenatal repair of open spina bifida (OSB). The main objective of this study was to report on our experience of treating twin pregnancies with OSB using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique. We also discuss reconsideration of the current exclusion criteria for fetal OSB repair. METHODS: Eight fetuses with OSB from seven twin pregnancies underwent successful prenatal repair. Six pregnancies were dichorionic diamniotic with only one twin affected, and one was monochorionic diamniotic with both twins affected. Percutaneous fetoscopy was performed under CO2 insufflation of the sac of the affected twin. Neurosurgical repair was performed using a biocellulose patch to protect the placode, with the skin sutured to hold the patch in place, with or without a myofascial flap. Neurodevelopment was assessed using the pediatric evaluation of disability inventory scale in babies older than 6 months of adjusted age, whereas the Alberta scale was used for babies younger than 6 months of adjusted age. RESULTS: All 14 fetuses were liveborn and none required additional repair. Gestational age at surgery ranged from 27.3 to 31.1 weeks, and gestational age at birth ranged from 31.6 to 36.0 weeks. Four out of eight affected twins developed sepsis, but had a good recovery. No sequela of prematurity was found in any of the unaffected twins. Short-term neurodevelopment was normal in all evaluated unaffected twins (5/5) and in all but one affected twins (7/8). In the affected group, only one baby required ventriculoperitoneal shunt placement. CONCLUSIONS: Prematurity is frequent after fetal surgery, and the risk is increased in twin pregnancy. Nevertheless, prenatal surgery using the SAFER technique is feasible, with low risk to both twins and their mother when performed by a highly experienced team. Long-term cognitive assessment of the unaffected twin is needed. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cutoff Points for Grip Strength in Screening for Sarcopenia in Community-Dwelling Older-Adults: A Systematic Review.

BACKGROUND: Currently, different cutoff points for handgrip strength (HGS) have been used to estimate the prevalence of sarcopenia. In addition, the variability of equipment and protocols for this assessment can significantly influence the early detection of this important public health problem. Thus, this review aims to identify the different cutoff points for HGS adopted for older men and women in screening for sarcopenia. OBJECTIVES: this review aims to identify the different cutoff points for HGS adopted for older men and women in screening for sarcopenia. METHODS: In accordance with the PRISMA 2020 recommendations, which included published studies from the last 10 years, from 6 databases, in 3 different languages. RESULTS: 19.730 references were identified, of which 62 were included for the review. All references analyzed used algorithms and definitions of sarcopenia already known in the literature. Of the studies found, 16 chose to develop cutoff values for HGS based on their own population. The variation in cutoff points was evident when compared between gender and regions of the world. CONCLUSION: It has become evident that there is a variability of normative values for HGS in sarcopenia screening. In addition, this systematic review shows the difference in the cutoff points used between the consensuses and those developed for each population.

Healthcare-associated infections: a threat to the survival of patients with COVID-19 in intensive care units.

BACKGROUND: Wide variation in mortality rates among critically ill patients with coronavirus disease 2019 (COVID-19) has been reported. This study evaluated whether healthcare-associated infections (HAI) are a risk factor for death among patients with severe COVID-19 in the intensive care unit (ICU). METHODS: This retrospective cohort study included patients with severe COVID-19 hospitalized in the ICU of four hospitals in the city of Curitiba, Brazil. Patients with COVID-19 who died during ICU hospitalization were compared with those who were discharged. A second analysis compared patients who developed HAI in the ICU with those who did not. Multiple logistic regression models were used to control for confounders. RESULTS: In total, 400 patients were included, and 123 (31%) patients developed HAI. The most common HAI was lower respiratory tract infection (67%). Independent risk factors for death were: age [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.43-2.15; P<0.0001]; clinical severity score (OR 2.21, 95% CI 1.70-2.87; P<0.0001); renal replacement therapy (OR 12.8, 95% CI 5.78-28.6; P<0.0001); and HAI (OR 5.9, 95% CI 3.31-10.5; P<0.0001). A longer interval between symptom onset and hospital admission was protective against death (OR 0.93, 95% CI 0.88-0.98; P=0.017). The only independent factors associated with HAI were high C-reactive protein and low PaO2/FiO2 ratio. CONCLUSIONS: No factors that could point to a high-risk group for HAI acquisition were identified. However, age, dialysis and HAI increased the risk of death in ICU patients with severe COVID-19; of these, HAI is the only preventable risk factor.

Recycling of Reinforced Glass Fibers Waste: Current Status.

In this paper, a review of the current status and future perspectives for reinforced glass fiber waste is undertaken, as well as an evaluation of the management hierarchy for these end-of-life materials. Waste levels are expected to increase in the coming years, but an improvement of collection routes is still necessary. The recycling processes for these materials are presented. The associated advantages and disadvantages, as well as the corresponding mechanical characteristics, are described. Although mechanical shredding is currently the most used process, there is a potential for thermal processes to be more competitive than others due to the fiber quality after the recycling process. However, the energy requirements of each of the processes are not yet well explained, which compromises the determination of the economic value of the recycled fibers when included in other products, as well as the process feasibility. Nevertheless, the work of some authors that successfully integrated recycled glass fibers into other elements with increased mechanical properties is evaluated. Future recommendations for the recycling of glass fiber and its commercialization are made.

Methoxpropamine (MXPr) in powder, urine and hair samples: Analytical characterization and metabolite identification of a new threat.

Methoxpropamine (MXPr) is an arylcyclohexylamine dissociative drug with structural similarities with 3-MeO-PCE, ketamine and deschloroketamine. MXPr was identified for the first time in Europe in October 2019 in Denmark and is considered a new psychoactive substance. We undertook the molecular identification and characterization of MXPr in urine, hair and powder samples. We used a combination of several analytical methods: liquid-state nuclear magnetic resonance (NMR), infra-red spectroscopy (IR) and liquid chromatography high-resolution mass spectrometry (LC-HRMS). The second objective was to explore the metabolism of MXPr in silico and in vitro. To detect characteristic metabolites that prove MXPr consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS). A software algorithm (Unifi®) was used to predict in silico biotransformations of MXPr. Three metabolites were identified in the in vitro studies including N-despropyl(nor)MXPr, O-desmethyl MXPr and dihydroMXPr. Most of these phase II metabolites were confirmed to be present in urine and hair samples collected from an MXPr consumer. This is the first report of the identification of MXPr in France with analytical findings. This study highlights the challenge of identifying new psychoactive substances (NPS) when they are missing from compound libraries and if a standard is not available. The use of various complementary analytical methods combined with HRMS offers a promising approach for the molecular characterization of NPS.

Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation.

BACKGROUND: Intervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP). IVD herniation involves cellular and extracellular matrix (ECM) alterations that have been associated with tissue fibrosis, although still poorly investigated. METHODS: Here, fibrotic alterations in human AF were evaluated, by characterizing the herniated ECM. Human AF samples (herniated lumbar IVD (n = 39, age 24-83) and scoliosis controls (n = 6, age 15-21)) were processed for transmission electron microscopy and histological/immunohistochemical analysis of fibrotic markers. Correlations between the fibrotic markers in AF ECM and the degree of NP containment (protused, contained and uncontained) and patients' age were conducted. RESULTS: Our results demonstrate that with herniation progression, i.e. loss of NP containment, human AF presents less stained area of sulphated glycosaminoglycans and collagen I, being collagen I fibres thinner and disorganized. On the other hand, fibronectin stained area and percentage of α-smooth muscle actin+ cells increase in human AF, while matrix metalloproteinase-12 (MMP12) production and percentage of macrophages (CD68+ cells) remain constant. These structural and biochemical fibrotic alterations observed in human AF with herniation progression occur independently of the age. CONCLUSIONS: The characterization of human AF here conducted evidence the presence of fibrosis in degenerated IVD, while highlighting the importance of considering the herniation progression stage, despite the patients' age, for a better understanding of the mechanisms behind AF failure and IVD herniation.

Cell wall polysaccharides from in vitro propagated Cereus hildmannianus K. Schum. plants.

Cereus hildmannianus is a cactus exhibiting morphological and physiological adaptation of its cladodes which ensuring growth in climatic and soil conditions unfavourable for many plant species. Currently, limited water resources and increasing demand for renewable energy make cacti a biomass source for the production of biofuels. Somaclones regenerated from callus in vitro can be a source of new raw material in useful plants. The objective of this work was to determine if the regenerated plants showing two different morphologies present polysaccharide composition different from the wild plant. Somaclones aqueous extraction shows the absence of soluble polysaccharides as mucilage. The alkaline extraction of in vivo cultivated plant showed the presence of starch, type I arabinogalactan, and arabinoxylan and the somaclones showed type I arabinogalactan and arabinoxylan in both morphologies. Hemicelluloses found in the somaclones are not different from in vivo cultivated plants, but somaclones not almost biosynthesize mucilage and starch.

Silk fibroin and sericin polymer blends for sustainable battery separators.

Natural polymers are a promising alternative for reducing the environmental impact of batteries. For this reason, it is still necessary to study their behavior and implement its use in these devices, especially in separator membranes. This work reports on new separator membranes based on silk fibroin (SF) and silk sericin (SS) prepared by salt leaching method. The effect of the different SS relative content on the physiochemical properties of the membranes and on the electrochemical performance of the corresponding batteries with lithium iron phosphate (LFP) as cathodes has been reported. It is observed that the increasing of SS content leads to a decrease of the overall crystallinity of the membranes. All SF/SS membranes presented a well-defined porosity above 75% with a uniform distribution of interconnected micropores. The electrolyte uptake and the ionic conductivity are dependent on the relative SS content. The addition of 10 wt% of SS into SF membranes, induce a high ionic conductivity of 4.09 mS.cm-1 and high lithium transference number (0.52), due to the improvement of the Li+ ions conduction paths within the blended structure. Charge/discharge tests performed in Lithium/C-LFP half-cells reveal a discharge capacity of 85 mAh.g-1 at 2C after 100 cycles for batteries with a SF/SS separator, containing a 10 wt% of SS, which suggests a stabilizing effect of Sericin on discharge capacity. Further, a 50% and 35% of capacity of retention and capacity fade, respectively, is observed. The presented SF/SS membrane show high electrochemical stability, being suitable for implementation in a next generation of sustainable battery systems. This could allow the SS valorization considering that 150,000 tons of SS are abandoned each year, reducing the contamination of environmental effluents.

Intervertebral disc decellularisation: progress and challenges.

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients' life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures.

Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1ß in a custom-made device. A 4 d treatment of the CTS + IL-1ß-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but also of tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1ß stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1ß and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1ß stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.

Patterned separator membranes with pillar surface microstructures for improved battery performance.

In order to improve battery performance by tuning battery separator membranes, this work reports on porous poly(vinylidene fluoride-co-trifluoroethylene) - P(VDF-TrFE)- membranes with surface pillar microstructures. Separators with tailored pillar diameter, height and bulk thickness were fabricated by template patterning and computer simulations, allowing to evaluate the effect of the pillar microstructure characteristics on battery performance. It is shown that the different pillar microstructures of the separators affect the uptake value (150-325%), ionic conductivity value (0.8-1.6 mS·cm-1) and discharge capacity of the lithium ion batteries (LIB) when compared with the separator without pillars. The experimental charge-discharge behavior demonstrates that the pillar parameters affect battery performance and the best microstructure leading to 80 mAh·g-1 at 2C. Battery performance can be thus optimized by adjusting pillar diameter, height and bulk thickness of the separators keeping its volume constant, as demonstrated also by the simulation results. The parameter with most influence in battery performance is the bulk thickness of the separator, allowing to obtain a maximum discharge capacity value of 117.8 mAh·g-1 at 90C for a thickness of 0.01 mm. Thus, this work shows that the optimization of the pillar microstructure of the separator membranes allows increasing the capacity towards a new generation of high-performance LIBs.

IL-1ß-pre-conditioned mesenchymal stem/stromal cells' secretome modulates the inflammatory response and aggrecan deposition in intervertebral disc.

Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1ß (10 ng/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1ß-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3α, IL-6, IL-8 and GRO α/ß/γ (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-γ, IL-10, IL-4, IL-5 and TNF-α (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/ cell-free therapeutic approach to LBP.