The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.

The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow-derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1-/- bone marrow-derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training.

OBJECTIVE: In this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodeling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice. METHODS: Combining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise. RESULTS: Muscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors including Nr4a3 and Ppargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of 'exercise-training' responsive genes shared for each tissue between genotypes. CONCLUSIONS: Our investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle and its likely impact on the system plays in the peripheral tissue adaptations to exercise training. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased gene expression signatures of inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.

Access to systemic treatment of non-melanoma skin cancer in Spain: a survey analysis.

BACKGROUND: Novel and highly effective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain's decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access. METHODS: A cross-sectional survey (July-September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs. FINDINGS: Fifty physicians from 15 Spanish AaCc responded to the survey. Access for drug with approved public reimbursement, Hedgehog inhibitors in basal-cell carcinoma and anti PD-L1 antibody in Merkel carcinoma, was observed in 84% and 86% of centers, respectively. For other EMA-approved treatments, but without reimbursement in Spain access decreased to 78% of centers. Heterogeneity in access was mainly observed intra regions. CONCLUSION: Unequal financial support for drugs for NMSC with creates a patchwork of access across Spanish hospitals, with variations even within the same AaCc.

Diversity of Orbiniella (Orbiniidae, Annelida) in the North Atlantic and the Arctic.

In this work, the diversity of the genus Orbiniella in the Nordic Seas and the North Atlantic waters south of Iceland is studied based on the analyses of molecular markers (mitochondrial COI, 16S rDNA and nuclear ITS2) and morphological characters. Our results showed the presence of at least five genetic lineages in the studied material which could also be morphologically identified by their segmental annulation patterns, the number and the shape of acicular spines, and the length and the shape of pygidial lobes. The species name Orbiniellapetersenae is assigned to one of the lineages restricting its geographical and vertical distribution to the deep-sea areas north of Iceland and Jan Mayen, and three lineages are described as new species (i.e., Orbiniellagriegi Meca & Budaeva, sp. nov., Orbiniellamayhemi Meca & Budaeva, sp. nov., and Orbiniellaparapari Meca & Budaeva, sp. nov.) elevating the number of known species in the genus to 25. Three deep-sea species of Orbiniella in our study are reported only north of the Greenland-Iceland-Scotland Ridge, one deep-sea species found south of the ridge. A single shallow-water species is distributed along the ridge and on the Norwegian shelf.

Specific Detection of Uropathogenic Escherichia coli via Fourier Transform Infrared Spectroscopy Using an Optical Biosensor.

Urinary tract infections (UTIs) are caused mainly by uropathogenic Escherichia coli (UPEC), accounting for both uncomplicated (75%) and complicated (65%) UTIs. Detecting UPEC in a specific, rapid, and timely manner is essential for eradication, and optical biosensors may be useful tools for detecting UPEC. Recently, biosensors have been developed for the selective detection of antigen-antibody-specific interactions. In this study, a methodology based on the principle of an optical biosensor was developed to identify specific biomolecules, such as the PapG protein, which is located at the tip of P fimbriae and promotes the interaction of UPEC with the uroepithelium of the human kidney during a UTI. For biosensor construction, recombinant PapG protein was generated and polyclonal anti-PapG antibodies were obtained. The biosensor was fabricated in silicon supports because its surface and anchor biomolecules can be modified through its various properties. The fabrication process was carried out using self-assembled monolayers (SAMs) and an immobilized bioreceptor (anti-PapG) to detect the PapG protein. Each stage of biosensor development was evaluated by Fourier transform infrared (FTIR) spectroscopy. The infrared spectra showed bands corresponding to the C-H, C=O, and amide II bonds, revealing the presence of the PapG protein. Then, the spectra of the second derivative were obtained from 1600 to 1700 cm-1 to specifically determine the interactions that occur in the secondary structures between the biological recognition element (anti-PapG antibodies) and the analyte (PapG protein) complex. The analyzed secondary structure showed ß-sheets and ß-turns during the detection of the PapG protein. Our data suggest that the PapG protein can be detected through an optical biosensor and that the biosensor exhibited high specificity for the detection of UPEC strains. Furthermore, these studies provide initial support for the development of more specific biosensors that can be applied in the future for the detection of clinical UPEC samples associated with ITUs.

Comparative study between Salkowski reagent and chromatographic method for auxins quantification from bacterial production.

Introduction: The Salkowski reagent method is a colorimetric technique used to determine auxin production, specifically as indole-3-acetic acid (IAA). It was developed to determine indoles rapidly; however, it does not follow Beer's law at high concentrations of IAA. Thus, there could be an overestimation of IAA with the Salkowski technique due to the detection of other indole compounds. Methods: This study aims to compare the Salkowski colorimetric method versus a chromatographic method to evidence the imprecision or overestimation obtained when auxins, such as indole-acetic acid (IAA), are determined as traits from promoting growth plant bacteria (PGPB), using ten different strains from three different isolation sources. The analysis used the same bacterial culture to compare the Salkowski colorimetric and chromatographic results. Each bacterium was cultivated in the modified TSA without or with tryptophan for 96 h. The same supernatant culture was used in both methods: Salkowski reagent and ultra-performance liquid chromatography coupled with a Mass Spectrometer (LC-MS/MS). Results: The first method indicated 5.4 to 27.4 mg L-1 without tryptophan in ten evaluated strains. When tryptophan was used as an inductor of auxin production, an increase was observed with an interval from 4.4 to 160 mg L-1. The principal auxin produced by all strains was IAA from that evaluated by the LC-MS/MS method, with significantly higher concentration with tryptophan addition than without. Strains belonging to the Kocuria genus were highlighted by high IAA production. The indole-3-propionic acid (IPA) was detected in all the bacterial cultures without tryptophan and only in K. turfanensis As05 with tryptophan, while it was not detected in other strains. In addition, indole-3-butyric acid (IBA) was detected at trace levels (13-16 µg L-1). Conclusions: The Salkowski reagent overestimates the IAA concentration with an interval of 41-1042 folds without tryptophan and 7-16330 folds with tryptophan as inductor. In future works, it will be necessary to determine IAA or other auxins using more suitable sensitive techniques and methodologies.

The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma.

Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin. This study is to examine the hypothesis that active plasma VWF directly influence fibrin polymerization and the structure of fibrin clots. The study used healthy and type 3 von Willebrand disease (VWD) plasma, purified plasma VWF, fibrin polymerization assays, confocal microscopy and scanning electron microscopy. The exposed A2 domain in active VWF harbors additional binding sites for fibrinogen, and significantly potentiates fibrin formation (P < 0.02). Antibody against the A2 domain of VWF significantly decreased the initial rate of change of fibrin formation (P < 0.002). Clot analyses revealed a significant difference in porosity between normal and type 3 VWD plasma (P < 0.008), further supported by scanning electron microscopy, which demonstrated thicker fibrin fibers in the presence of plasma VWF (P < 0.0003). Confocal immunofluorescence microscopy showed punctate VWF staining along fibrin fibrils, providing visual evidence of the integration of plasma VWF into the fibrin matrix. The study with type 3 VWD plasma supports the hypothesis that plasma VWF directly influences fibrin polymerization and clot structure. In addition, a conformational change in the A1A2 domains exposes a hidden fibrin(ogen) binding site, indicating that plasma VWF determines the fibrin clot structure.

Facile synthesis of silver doped manganese oxide nanocomposite with superior photocatalytic and antimicrobial activity under visible spectrum.

Water pollution and antimicrobial resistance (AMR) have become two global threats; 80% of diseases and 50% of child deaths are due to poor water quality. In this study, hydrothermal processing was employed to manufacture manganese oxide nanorods. Silver dopant was deposited on the surface of manganese oxide. XRD diffractogram confirmed the facile synthesis of Ag/Mn2O3 nanocomposite. XPS survey analysis demonstrated silver content of 9.43 atom %. Photocatalytic measurements demonstrated the outstanding efficiency of the Ag-Mn2O3 compared to virgin oxide particles under visible radiation. Degradation efficiencies Mn2O3 and Ag/Mn2O3 on methyl orange (MO) dye was found to be 53% and 85% under visible spectrum. Silver dopant was found to decrease the binding energy of valence electrons; this action could support electron-hole pair generation under visible spectrum and could promote catalytic performance. Ag/Mn2O3 NPs demonstrated most effective performance (95% removal efficiency) at pH 3; this could be ascribed to the electrostatic attraction between positively charged catalyst and the negatively charged MO. Ag/Mn2O3 demonstrated enhanced antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) (19 mm ZOI), and Gram-negative Escherichia coli (E. coli) (22 mm ZOI) respectively; the developed nanocomposite demonstrated advanced anti-film activity with inhibition percentage of 95.5% against E. coli followed by 89.5% against S. aureus.

Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site.

Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.

Metastatic Bladder Urothelial Carcinoma Masquerading as Myositis.

Skeletal muscle metastases are uncommon, and metastases of urothelial carcinoma to the skeletal muscle are particularly rare. The most common presentation of skeletal muscle metastases is a focal mass, but their clinical and radiographic findings can be diverse. We present an unusual case of a 71-year-old male without prior known history of malignancy who presented with skeletal muscle pain with imaging most consistent with an inflammatory or infectious process but was ultimately determined to be metastatic urothelial carcinoma from the bladder. This case demonstrates the need to keep an expanded differential for muscular pain, particularly when initial treatments are ineffective.

Updating and profiling the natural product-likeness of Latin American compound libraries.

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

Understanding the Decamethylferrocene FeIII/IV Oxidation Process in Tris(pentafluoroethyl)trifluorophosphate-Containing Ionic Liquids at Glassy Carbon and Boron-Doped Diamond Electrodes.

Under voltammetric conditions, the neutral decamethylferrocene ([Me10Fc]) to cationic ([Me10Fc]+) FeII/III process is a well-known reversible outer-sphere reaction. A companion cationic [Me10Fc]+ to dicationic [Me10Fc]2+ FeIII/IV process has been reported under direct current (DC) cyclic voltammetric conditions at highly positive potentials in liquid SO2 at low temperatures and in a 1.5:1.0 AlCl3/1-butylpyridinium chloride melt. This study demonstrates that in room-temperature ionic liquids containing the hard to oxidize and hydrophobic tris(pentafluoroethyl)trifluorophosphate anion, the [Me10Fc]+/2+ process can be detected as a quasi-reversible reaction at glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Large amplitude Fourier-transformed alternating current (FT-AC) voltammetry minimizes background current contributions occurring at potentials similar to those of the FeIII/IV process in the second and higher-order harmonics. This enables a straightforward determination of the thermodynamics and kinetics for both the FeII/III and FeIII/IV processes. Unlike the ideal outer-sphere FeII/III process, the parameters of the FeIII/IV process may be impacted by ion-interaction effects. For the faster FeII/III process, heterogeneous rate constants are approximately 10 times smaller at BDD than those at GC electrodes. This electrode dependence is less pronounced for the slower FeIII/IV process. The slower BDD kinetics may be attributed in part to a density of states lower than that at GC.

Zinc-Catalyzed Cyclization of Alkynyl Derivatives: Substrate Scope and Mechanistic Insights.

Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.

Magnetic motors in interphases: Motion control and integration in soft robots.

Magnetic motors are a class of out-of-equilibrium particles that exhibit controlled and fast motion overcoming Brownian fluctuations by harnessing external magnetic fields. The advances in this field resulted in motors that have been used for different applications, such as biomedicine or environmental remediation. In this Perspective, an overview of the recent advancements of magnetic motors is provided, with a special focus on controlled motion. This aspect extends from trapping, steering, and guidance to organized motor grouping and degrouping, which is known as swarm control. Further, the integration of magnetic motors in soft robots to actuate their motion is also discussed. Finally, some remarks and perspectives of the field are outlined.

Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria.

Purines and their derivatives control intracellular energy homeostasis and nucleotide synthesis, and act as signaling molecules. Here, we combine structural and sequence information to define a purine-binding motif that is present in sensor domains of thousands of bacterial receptors that modulate motility, gene expression, metabolism, and second-messenger turnover. Microcalorimetric titrations of selected sensor domains validate their ability to specifically bind purine derivatives, and evolutionary analyses indicate that purine sensors share a common ancestor with amino-acid receptors. Furthermore, we provide experimental evidence of physiological relevance of purine sensing in a second-messenger signaling system that modulates c-di-GMP levels.

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FK506-binding protein 12 when the transcription of FBXO22 gene is activated. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in F-box protein 22 (FBXO22) to achieve target degradation. Lastly, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading additional endogenous proteins, including bromodomain-containing protein 4 and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein.

Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes.

Tolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce identical behavioral effects. Tolerance is not well-understood, and numerous researchers have turned to model organisms, particularly Drosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease-causing genes between flies and humans, including those associated with Alcohol Use Disorder. Numerous Drosophila tolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we analyzed our own, as well as data published by other labs to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many 'perceived' tolerance phenotypes, thus classifying such mutants as 'secondary' tolerance mutants. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. These residuals provide predictive insight into the likelihood of a mutant being a 'primary' tolerance mutant, where a tolerance phenotype is not solely a consequence of initial resistance, and we offer a framework for understanding the relationship between initial resistance and tolerance.

Dynamic Adhesive Behavior and Biofilm Formation of Staphylococcus aureus on Polylactic Acid Surfaces in Diabetic Environments.

Interest in biodegradable implants has focused attention on the resorbable polymer polylactic acid. However, the risk of these materials promoting infection, especially in patients with existing pathologies, needs to be monitored. The enrichment of a bacterial adhesion medium with compounds that are associated with human pathologies can help in understanding how these components affect the development of infectious processes. Specifically, this work evaluates the influence of glucose and ketone bodies (in a diabetic context) on the adhesion dynamics of S. aureus to the biomaterial polylactic acid, employing different approaches and discussing the results based on the physical properties of the bacterial surface and its metabolic activity. The combination of ketoacidosis and hyperglycemia (GK2) appears to be the worst scenario: this system promotes a state of continuous bacterial colonization over time, suppressing the stationary phase of adhesion and strengthening the attachment of bacteria to the surface. In addition, these supplements cause a significant increase in the metabolic activity of the bacteria. Compared to non-enriched media, biofilm formation doubles under ketoacidosis conditions, while in the planktonic state, it is glucose that triggers metabolic activity, which is practically suppressed when only ketone components are present. Both information must be complementary to understand what can happen in a real system, where planktonic bacteria are the ones that initially colonize a surface, and, subsequently, these attached bacteria end up forming a biofilm. This information highlights the need for good monitoring of diabetic patients, especially if they use an implanted device made of PLA.

Performance of the First-Trimester Cervical Consistency Index to Predict Preterm Birth.

Background/Objectives: Preterm birth (PTB) remains a significant global health challenge. Previous attempts to predict preterm birth in the first trimester using cervical length have been contradictory. The cervical consistency index (CCI) was introduced to quantify early cervical changes and has shown promise across various clinical scenarios in the mid-trimester, though testing in the first trimester is lacking. This study aims to assess the cervical consistency index performance in predicting preterm birth during the first trimester of pregnancy. Methods: In this prospective cohort study, focused exclusively on research, women with singleton pregnancies, both with and without a history of spontaneous preterm birth (sPTB), were included. The primary outcome was sPTB before 37 weeks, with a secondary outcome of sPTB before 34 weeks. CCI measurements were taken between 11+0 to 13+6 weeks of gestation. Receiver operating characteristic (ROC) curves were generated, and sensitivity and specificity were calculated for the optimal cut-off and for the 5th, 10th, and 15th percentile. Intraobserver and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). Results: Among the 667 patients analyzed, the rates of sPTB before 37 and 34 weeks were 9.2% (61/667) and 1.8% (12/667), respectively. The detection rates (DRs) for CCI predicting PTB before 37 and 34 weeks were 19.7% (12/61) and 33.3% (4/12). Negative predictive values were 91.8% (546/595) and 98.7% (588/596), while the areas under the curve (AUC) for sPTB before 37 and 34 weeks were 0.62 (95% CI: 0.54-0.69) and 0.80 (95% CI: 0.71-0.89), respectively. Of the 61 patients with preterm birth, 13 (21.3%) had a preterm birth history; in this group, the CCI percentile 10th identified 39% (5/13). Intraobserver ICC was 0.862 (95% CI: 0.769-0.920), and interobserver ICC was 0.833 (95% CI: 0.722-0.902). Conclusions: This study suggests that utilizing CCI in the first trimester of pregnancy could serve as a valuable tool for predicting preterm birth before 34 weeks of gestation, demonstrating robust intraobserver and interobserver reliability.

Screen exposure, mental health and emotional well-being in the adolescent population: is it time for governments to take action?

During the last decade, a multitude of epidemiological studies with different designs have been published assessing the association between the use of digital media and psychological well-being, including the incidence of mental disorders and suicidal behaviours. Particularly, available research has very often focused on smartphone use in teenagers, with highly addictive potential, coining the term 'problematic smartphone use' and developing specific scales to measure the addictive or problematic use of smartphones. Available studies, despite some methodological limitations and gaps in knowledge, suggest that higher screen time is associated with impaired psychological well-being, lower self-esteem, higher levels of body dissatisfaction, higher incidence of eating disorders, poorer sleeping outcomes and higher odds of depressive symptoms in adolescents. Moreover, a significant association has also been found between screen time and higher suicide risk. Finally, problematic pornography has been shown to be highly prevalent and it is a strong cause of concern to many public health departments and national governments because it might be eventually associated with aggressive sexual behaviours.