Molecular Visualization of Neuronal TDP43 Pathology In Situ.

Nuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death. Here, we show that adding small monovalent oligonucleotides successfully recapitulates pathological TDP43 mislocalization and aggregation in iPSC-derived neurons (iNeurons). By employing a multimodal in situ cryo-correlative light and electron microscopy pipeline, we examine how RNA influences the localization and aggregation of TDP43 in near-native conditions. We find that mislocalized TDP43 forms ordered fibrils within lysosomes and autophagosomes in iNeurons as well as in patient tissue, and provide the first high-resolution snapshots of TDP43 aggregates in situ. In so doing, we provide a cellular model for studying initial pathogenic events underlying ALS, FTLD, and related TDP43-proteinopathies.

Neuromodulation of Executive Dysfunction in Patients with Acute Stroke Using Transcranial Direct Current Stimulation: Study Protocol for a Triple-Blind, Randomized Sham-Controlled Trial.

Research on the benefits of non-invasive brain stimulation in stroke patients to improve executive functions is scarce. The objective of this study was to investigate the effectiveness of transcranial direct current stimulation (tDCS) in combination with cognitive training for the rehabilitation of executive functions in acute and subacute stroke patients as well as to explore the underlying physiological mechanisms. A triple-blinded, randomized-controlled clinical trial will be conducted involving 60 stroke patients with frontal or basal ganglia lesions and a Montreal Cognitive Assessment (MoCA) score less than 26. Participants will be randomly assigned to receive active tDCS (anode over the left dorsolateral prefrontal cortex, cathode at the right supraorbital region, 20 min at 2 mA) or sham tDCS in a 1:1 ratio for 10 sessions, followed by targeted executive function training. The primary efficacy outcome will be the MoCA score, while secondary outcomes will include the five-digit test (inhibitory control), the Digit Span Task (working memory), the abbreviated version of the Wisconsin Card Sorting test (cognitive flexibility), modified Rankin scale (functional state), Beck-II depression inventory, apathy evaluation scale, and the WHOQOL-BREF (quality of life), assessed immediately after the intervention and at 1, 3, 6, and 12 months post-intervention. Additionally, resting-state functional connectivity and blood biomarkers, such as neurotrophins, growth factors, and inflammatory molecules, will be evaluated before and after the intervention. This study will contribute to the investigation of the efficacy of tDCS in rehabilitating executive functions in acute and subacute stroke patients. The multidimensional approach utilized in this study, which includes analysis of resting-state connectivity and neuroplasticity-related blood biomarkers, is expected to provide insights into the underlying brain mechanisms involved in the rehabilitation of dysexecutive syndrome.

Efficiency of the zinc chelator 1,10-phenanthroline for assisted oocyte activation following ICSI in pigs.

Context In vitro embryo production in pigs is an important tool for advancing biomedical research. Intracytoplasmic sperm injection (ICSI) circumvents the polyspermy problems associated with conventional IVF in porcine. However, the suboptimal efficiency for ICSI in pigs requires new strategies to increase blastocyst formation rates. Aim To investigate novel methods for assisted activation using the zinc chelator 1,10-phenanthroline (PHEN), and to improve embryo developmental competence and quality of ICSI porcine blastocyst. Methods ICSI embryos were treated with PHEN after or before sperm injection, recording pronuclear formation, blastocyst rate and the expression of SMARCA4, OCT4, SOX2 and CDX2. Key results Neither electrical nor PHEN significantly improves pronuclear formation rates before or after ICSI. Following in vitro culture to the blastocyst stage, no significant differences were observed in developmental rates among the groups. Moreover, the use of PHEN did not alter the total cell number or the expression of OCT4, SOX2 and CDX2 in pig ICSI blastocysts. Conclusions Assisted oocyte activation with PHEN does not affect the preimplantation development of ICSI-derived pig embryos. Implications These results hold significance in refining and advancing the application of assisted oocyte activation techniques. They offer insights into addressing fertility issues and propelling advancements in human and animal reproductive medicine.

Effect of Preoperative Administration of Dexamethasone vs. Methylprednisolone in Surgical Extraction of Impacted Lower Third Molars: Randomized Controlled Clinical Trial.

Background/Objectives: Glucocorticoids are drugs that are increasingly used in oral surgery to reduce trismus, inflammation, and postoperative pain, three frequent complications after the surgical extraction of impacted lower third molars. The aim of this study was to compare the effect of 8 mg dexamethasone versus 40 mg methylprednisolone in the prevention of postoperative complications after third molar surgery. Methods: A randomized double-blind clinical trial was conducted following CONSORT guidelines. In detail, 84 patients were included in the study, who randomly received a single preoperative submucosal dose of dexamethasone (8 mg) or methylprednisolone (40 mg). The variables analyzed, as primary outcomes, were trismus, inflammation, and postoperative pain. The measurements were performed at baseline (0 h), 3 h, 7 h, 24 h, 48 h, and 7 th day using a Visual Analog Scale (VAS), Verbal Rating Scale (VRS), and the Gabka-Matsumara method. Results: Dexamethasone reduced trismus, inflammation, and postoperative pain significantly better than methylprednisolone. Conclusions: Preoperative submucosal administration of 8 mg dexamethasone is effective and safe in reducing the severity of postoperative complications following surgical extraction of impacted lower third molars.

Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.

Parasitic diseases, particularly malaria (caused by Plasmodium falciparum) and theileriosis (caused by Theileria spp.), profoundly impact global health and the socioeconomic well-being of lower-income countries. Despite recent advances, identifying host metabolic proteins essential for these auxotrophic pathogens remains challenging. Here, we generate a novel metabolic model of human hepatocytes infected with P. falciparum and integrate it with a genome-wide CRISPR knockout screen targeting Theileria-infected cells to pinpoint shared vulnerabilities. We identify key host metabolic enzymes critical for the intracellular survival of both of these lethal hemoparasites. Remarkably, among the metabolic proteins identified by our synergistic approach, we find that host purine and heme biosynthetic enzymes are essential for the intracellular survival of P. falciparum and Theileria, while other host enzymes are only essential under certain metabolic conditions, highlighting P. falciparum's adaptability and ability to scavenge nutrients selectively. Unexpectedly, host porphyrins emerge as being essential for both parasites. The shared vulnerabilities open new avenues for developing more effective therapies against these debilitating diseases, with the potential for broader applicability in combating apicomplexan infections.

Social determinants of health influencing the choice of dialysis modality in advanced chronic kidney disease: Need of an interdisciplinary approach.

INTRODUCTION: The influence of socioeconomic and cultural barriers in the choice of renal replacement therapy (RRT) techniques in advanced chronic kidney disease (ACKD) has been scarcely explored, which can generate problems of inequity, frequently unnoticed in health care. The aim of this study is to identify the "non-medical" barriers that influence the choice of RRT in an advanced chronic kidney disease (ACKD) consultation in Spain. MATERIAL AND METHODS: Retrospective analysis including the total number of patients seen in the ACKD consultation in a tertiary hospital from 2009 to 2020. Inclusion in the ACKD consultation began with an eligibility test and a decision-making process, conducted by a specifically trained nurse. The variables considered for the study were: age, sex, etiology of CKD, level of dependence for basic activities of daily living (Barthel Scale) and instrumental activities of daily living (Lawton and Brody Scale), Spanish versus foreign nationality, socioeconomic level and language barrier. The socioeconomic level was extrapolated according to home and health district by primary care center to which the patients belonged. RESULTS: A total of 673 persons were seen in the ACKD consultation during the study period, of whom 400 (59.4%) opted for hemodialysis (HD), 156 (23.1%) for peritoneal dialysis (PD), 4 (0.5%) for early living donor renal transplantation (LDRT) and 113 (16.7%) chose conservative care (CC). The choice of PD as the chosen RRT technique (vs. HD) was associated with people with a high socioeconomic level (38.7% vs. 22.5%) (p = 0.002), Spanish nationality (91% vs. 77.7%) (p < 0.001), to a lower language barrier (0.6% vs 10.5%) (p < 0.001), and to a higher score on the Barthel scale (97.4 vs 92.9) and on the Lawton and Brody scale (7 vs 6.1) (p < 0.001). Neither age nor sex showed significant differences in the choice of both techniques. Patients who opted for CC were significantly older (81.1 vs 67.7 years; p < 0.001), more dependent (p < 0.001), with a higher proportion of women (49.6% vs 35.2%; p = 0.006) and a higher proportion of Spaniards (94.7% vs 81%, p = 0.001) in relation to the choice of other techniques (PD and HD). Socioeconomic level did not influence the choice of CC. CONCLUSION: Despite a regulated decision-making process, there are factors such as socioeconomic status, migration, language barrier and dependency of the population that influence the type of RRT chosen. To address these aspects that may cause inequity, an intersectoral and multilevel intervention is required with interdisciplinary teams that include, among others, social workers, to provide a more holistic and person-centered assessment.

RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.

INF2 formin variants linked to human inherited kidney disease reprogram the transcriptome, causing mitotic chaos and cell death.

Mutations in the human INF2 gene cause autosomal dominant focal segmental glomerulosclerosis (FSGS)-a condition characterized by podocyte loss, scarring, and subsequent kidney degeneration. To understand INF2-linked pathogenicity, we examined the effect of pathogenic INF2 on renal epithelial cell lines and human primary podocytes. Our study revealed an increased incidence of mitotic cells with surplus microtubule-organizing centers fostering multipolar spindle assembly, leading to nuclear abnormalities, particularly multi-micronucleation. The levels of expression of exogenous pathogenic INF2 were similar to those of endogenous INF2. The aberrant nuclear phenotypes were observed regardless of the expression method used (retrovirus infection or plasmid transfection) or the promoter (LTR or CMV) used, and were absent with exogenous wild type INF2 expression. This indicates that the effect of pathogenic INF2 is not due to overexpression or experimental cell manipulation, but instead to the intrinsic properties of pathogenic INF2. Inactivation of the INF2 catalytic domain prevented aberrant nuclei formation. Pathogenic INF2 triggered the translocation of the transcriptional cofactor MRTF into the nucleus. RNA sequencing revealed a profound alteration in the transcriptome that could be primarily attributed to the sustained activation of the MRTF-SRF transcriptional complex. Cells eventually underwent mitotic catastrophe and death. Reducing MRTF-SRF activation mitigated multi-micronucleation, reducing the extent of cell death. Our results, if validated in animal models, could provide insights into the mechanism driving glomerular degeneration in INF2-linked FSGS and may suggest potential therapeutic strategies for impeding FSGS progression.

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Forecast Cosmological Constraints with the 1D Wavelet Scattering Transform and the Lyman-α Forest.

We make forecasts for the constraining power of the 1D wavelet scattering transform when used with a Lyman-α forest cosmology survey. Using mock simulations and a Fisher matrix, we show that there is considerable cosmological information in the scattering transform coefficients not captured by the flux power spectrum. We estimate mock covariance matrices assuming uncorrelated Gaussian pixel noise for each quasar at a level drawn from a simple log-normal model. The extra information comes from a smaller estimated covariance in the first-order wavelet power and from second-order wavelet coefficients that probe non-Gaussian information in the forest. Forecast constraints on cosmological parameters from the wavelet scattering transform are more than an order of magnitude tighter than for the power spectrum, shrinking a 4D parameter space by a factor of 10^{6}. Should these improvements be realized with the Dark Energy Spectroscopic Instrument, inflationary running would be constrained to test common inflationary models predicting α_{s}=-6×10^{-4} and neutrino mass constraints would be improved enough for a 5-σ detection of the minimal neutrino mass.

Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation.

Acute inflammation, characterized by a rapid influx of neutrophils, is a protective response that can lead to chronic inflammatory diseases when left unresolved. Secretion of LTB 4 -containing exosomes is required for effective neutrophil infiltration during inflammation. In this study, we show that neutrophils release nuclear DNA in a non-lytic, rapid, and repetitive manner, via a mechanism distinct from suicidal NET release and cell death. The packaging of nuclear DNA occurs in the lumen of nuclear envelope (NE)-derived multivesicular bodies (MVBs) that harbor the LTB 4 synthesizing machinery and is mediated by the lamin B receptor (LBR) and chromatin decondensation. Disruption of secreted exosome-associated DNA (SEAD) in a model of sterile inflammation in mouse skin amplifies and prolongs the presence of neutrophils, impeding the onset of resolution. Together, these findings advance our understanding of neutrophil functions during inflammation and the physiological significance of NETs, with implications for novel treatments for inflammatory disorders.

Thrombus discrimination with electron density: potential implications for non-contrast computed tomography imaging.

The potential clinical usefulness of electron density (ED) imaging, that can be directly estimated using dual-layer spectral computed tomography (CT), has been poorly investigated. We explored whether ED imaging might improve thrombus identification compared to conventional imaging in vitro. We evaluated mechanical thrombectomy material obtained from patients with acute ischemic stroke (AIS) treated in a tertiary level stroke center and immediately fixed in 10% neutral buffered formalin and stored in polystyrene test tubes. The test tubes were immersed in a bucket of water for evaluation by spectral CT, along with scattered control tubes. All images were obtained using a dual-layer detector CT scanner. Each tube was assessed using multiparametric side-by-side view of conventional CT (120 kVp), low monoenergetic imaging (40 keV), and ED images. Fifty-eight polystyrene tubes were analyzed, comprising 52 tubes with thrombectomy material of at least 1 mm2 size obtained from 52 AIS patients, and six control tubes filled with formalin. ED imaging identified accurately the presence of material in all tubes, whereas 2 (3%) of the tubes containing thrombus were not identified by conventional CT, leading to a very good agreement between observers for the presence of material using conventional CT and ED imaging (kappa =0.84, P<0.001). Using ED imaging, thrombus material showed a mean density of 108.8±2.9 percent ED relative to water (%EDW), water had a mean density of 100.0±0.3 %EDW, and formalin a mean density of 103.5±1.2 %EDW. Compared to conventional imaging and 40 keV monoenergetic, ED imaging had a significantly higher signal-to-noise ratio (conventional 10.4±7.0, vs. 40 keV 11.5±8.4, vs. ED 490.0±304.5, P<0.001) and contrast-to-noise ratio (CNR) (conventional 4.3±4.3, vs. 40 keV 5.7±11.2, vs. ED 37.8±29.1, P<0.001). In this in-vitro study, we demonstrated improved visualization of thrombus with ED imaging compared to conventional imaging and low monoenergetic imaging, with a significant increase in CNR.

H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours.

Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair.

Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice.

BACKGROUND: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. METHODS: Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7:Cx3cr1-Cre) or neurons (P2rx7:Thy-1-Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RESULTS: RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a, a model of Dravet syndrome. CONCLUSIONS: Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy.

Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.

According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.

Barriers and enablers to people-centred viral hepatitis care in Vietnam and the Philippines: Results of a patient journey mapping study.

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.

Market analysis of the presence of endocrine disrupting chemicals in cosmetic products intended for oncological patients and other vulnerable groups.

There is growing concern about the presence of endocrine disrupting chemicals (EDCs) in cosmetics. We aimed to identify the main cosmetic ingredients with suspected endocrine-disrupting properties, and analyse their presence in current marketed products. Particular attention was given to products intended for susceptible (due to physiological status) and vulnerable (due to specific pathologies) groups with a view to informing cosmetologists and related health professionals of the scientific basis and current status of any concerns. Suspected EDCs used as cosmetic ingredients, included in lists published by regulatory agencies, were documented and investigated by weight of evidence analysis based on endocrine-related toxicity studies. In total, 49 suspected EDCs were identified from a sample of over a thousand cosmetic products marketed in the European Union. Suspected EDCs were found in approximately one third of products, with a similar frequency in products intended for susceptible and vulnerable groups. Avobenzone (CAS number:70356-09-1), octisalate (CAS number: 118-60-5), and butylated hydroxytoluene (CAS number: 128-37-0) were mostly commonly identified. The presence of EDCs was particularly high for sun care cosmetic products. Our results highlight potentially significant exposure through cosmetics to substances currently studied by regulatory institutions as suspected endocrine disrupters. EDCs are not yet universally regulated, and informing health professionals and educating the population as a precaution are options to reduce individual exposure levels, especially in vulnerable and susceptible groups. Special recommendations are needed for products intended for oncological patients.

Novel Biomarkers of Bone Metabolism.

Bone represents a metabolically active tissue subject to continuous remodeling orchestrated by the dynamic interplay between osteoblasts and osteoclasts. These cellular processes are modulated by a complex interplay of biochemical and mechanical factors, which are instrumental in assessing bone remodeling. This comprehensive evaluation aids in detecting disorders arising from imbalances between bone formation and reabsorption. Osteoporosis, characterized by a reduction in bone mass and strength leading to heightened bone fragility and susceptibility to fractures, is one of the more prevalent chronic diseases. Some epidemiological studies, especially in patients with chronic kidney disease (CKD), have identified an association between osteoporosis and vascular calcification. Notably, low bone mineral density has been linked to an increased incidence of aortic calcification, with shared molecules, mechanisms, and pathways between the two processes. Certain molecules emerging from these shared pathways can serve as biomarkers for bone and mineral metabolism. Detecting and evaluating these alterations early is crucial, requiring the identification of biomarkers that are reliable for early intervention. While traditional biomarkers for bone remodeling and vascular calcification exist, they suffer from limitations such as low specificity, low sensitivity, and conflicting results across studies. In response, efforts are underway to explore new, more specific biomarkers that can detect alterations at earlier stages. The aim of this review is to comprehensively examine some of the emerging biomarkers in mineral metabolism and their correlation with bone mineral density, fracture risk, and vascular calcification as well as their potential use in clinical practice.

Household mixed plastic waste derived adsorbents for CO2 capture: A feasibility study.

The feasibility of producing activated carbon (AC) from real Household Mixed Plastic Waste (HMPW) comprising of LDPE, HDPE, PP, PS, and PET for carbon capture via direct carbonisation followed by microwave-assisted or conventional thermally assisted chemical activation was investigated. A microwave-assisted activation procedure was adopted to assess the impact on the CO2 capture capacity of the resulting AC using both a lower temperature (400 °C vs. 700 °C) and a shorter duration (5 vs. 120 mins) than that required for conventional activation. The results obtained showed that the AC yield was 71 and 78% for the conventional and microwave-assisted samples, respectively. Microwave activation consumed five-fold less energy (0.19 kWh) than the conventional activation (0.98 kWh). Thermal stability results indicated total weight loss of 10.0 and 8.3 wt%, respectively, for conventional and microwave-activated samples over the temperature range of 25-1000 °C, with ACs from both activation routes displaying a type 1 nitrogen isotherm. The dynamic CO2 uptake capacity at 1 bar and 25 °C was 1.53 mmol/g, with maximum equilibrium uptake ranging between 1.32 and 2.39 mmol/g at temperatures (0-50 °C) and 1 bar for the conventionally activated AC. The analogous microwave-activated sample showed a higher dynamic CO2 uptake of 1.62 mmol/g and equilibrium uptake in the range 1.58-2.88 mmol/g under equivalent conditions. The results therefore indicate that microwave activation results in enhanced carbon capture potential. To the best of our knowledge, this is the first-time microwave heating has been employed to convert household mixed plastic wastes directly into ACs for carbon capture applications. This report therefore demonstrates that the management of mixed plastics could lead to the development of a circular economy through the conversion of waste into value-added materials.