Di(pyridin-2-yl)amino-substituted 1,10-phenanthrolines and their Ru(II)-Pd(II) dinuclear complexes: synthesis, characterization and application in Cu-free Sonogashira reaction.

Dinuclear complexes bearing Ru(II) photoactive centers are of interest for the development of efficient dual catalysts for many photocatalyzed reactions. Ditopic polypyridine ligands, bis(pyridin-2-yl)amino-1,10-phenanthrolines, containing an additional coordination site (bis(pyridin-2-yl)amine, dpa) at positions 3, 4 or 5 of the 1,10-phenanthroline core (Phen-3NPy2, Phen-4NPy2 and Phen-5NPy2) were synthesized. They were used as bridging ligands to obtain dinuclear complexes [(bpy)2Ru(Phen-NPy2)PdCl2](PF6)2 (Ru(Phen-NPy2)Pd) in good yields via stepwise complexation. In these complexes Ru(II) is coordinated to 1,10-phenanthroline, while Pd(II) is bound to the dpa chelating moiety, as established by NMR spectroscopy and X-ray single crystal analysis. The influence of the position of dpa in the phenanthroline ring on the structural, optical and electrochemical properties of Ru(Phen-NPy2)Pd complexes was studied. The complexes exhibit photoluminescence in argon-saturated MeCN solution with maxima in the range of 615-625 nm, with emission quantum yields ranging from 0.11 to 0.15 for Ru(Phen-NPy2) complexes and from 0.018 to 0.026 for dinuclear Ru(Phen-NPy2)Pd complexes. All the complexes absorb visible light in the range of 370-470 nm with high extinction coefficients and can be considered useful as photocatalysts. The Ru2+/3+ potential in Ru(Phen-NPy2)Pd complexes showed no significant dependence on the dpa position, while the Pd2+/0 reduction potential was significantly lower for Ru(Phen-3NPy2)Pd and Ru(Phen-4NPy2)Pd, than for Ru(Phen-5NPy2)Pd (-0.57 V and -0.72 V vs. Ag/AgCl, KCl(sat.), respectively). The complexes were used as photoactivated precatalysts in Cu-free Sonogashira coupling under blue LEDs (12 W) irradiation. The reaction proceeded roughly three times faster when Ru(Phen-4NPy2)Pd and Ru(Phen-3NPy2)Pd were used as catalyst precursors compared to the mixed catalytic system Ru(bpy)3(PF6)2/(RNPy2)PdCl2.

The influence of simultaneous posterior colporrhaphy and perineoplasty on the efficiency and safety of mesh-augmented sacrospinal fixation (apical sling) in advanced POP repair.

BACKGROUND: Pelvic organ prolapse (POP) is one of the most common pathologies of the pelvic floor, and it can be found among 40-60% of women who have given birth. Correction of the defect of the DeLancey level II without reconstruction of the apical defect is doomed to failure. Also, in the structure of pelvic floor defects, there is often an incompetency of the perineal body, as a consequence of traumatic delivery. Perineoplasty is considered to be the main method of correction for perineal body incompetency. However, it is worth mentioning that there are no randomized trials, which estimate the influence of simultaneous correction of the perineal body on the effectiveness of transvaginal apical fixation. METHODS: It is planned to include 310 patients in this trial. Patients who met the inclusion/exclusion criteria will be randomized into 2 groups: 1st group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy without perineoplasty, 2nd group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy and perineoplasty. Patients will be called to an appointment 6, 12, and 24 months after discharge. DISCUSSION: The aim of this trial is to evaluate the efficiency and safety of simultaneous perineoplasty on the clinical and anatomical efficacy of mesh-augmented sacrospinal fixation in advanced pelvic organ prolapse repair. Based on previous studies, it was difficult to estimate and comprehend whether colpoperinoplasty actually reduces the risk of prolapse recurrence. TRIAL REGISTRATION: NCT05422209. Registered on 18 May 2022.

Cytocompatible Hydrogels with Tunable Mechanical Strength and Adjustable Swelling Properties through Photo-Cross-Linking of Poly(vinylphosphonates).

Herein, the synthesis, characterization, and application of a novel synthetic hydrogel based on the photoinitiated cross-linking of poly(vinylphosphonates) is presented. First, statistical copolymers with adjustable ratios of the monomers diallyl vinylphosphonate (DAlVP) and diethyl vinylphosphonate (DEVP), as well as different molecular weights, were obtained via rare earth metal-mediated group-transfer polymerization (REM-GTP) while maintaining narrow polydispersities. The copolymers were cross-linked by applying photoinitiated thiol-ene click chemistry (λ = 365 nm). The network formation was monitored via oscillatory rheology coupled with UV-irradiation, revealing the high spatiotemporal control of the reaction. Moreover, the equilibrium storage moduli of poly(vinylphosphonate)-based hydrogels increased with a growing number of DAlVP units and upon application of a different cross-linker, which was additionally confirmed by nanoindentation experiments. In contrast, the water uptake of hydrogels decreased with higher DAlVP amounts in the corresponding hydrogels due to lower chain mobility and an overall increase in the hydrophobicity of the samples. Upon successful functionalization of P(DEVP-stat-DAlVP) copolymers with sodium 3-mercaptopropane-1-sulfonate, as indicated via 1H DOSY NMR, the respective cross-linked materials displayed a remarkable increase in the water uptake; thus, presenting highly hydrophilic gels with an apparent interplay between water uptake, cross-linking density, and functionalization degree. Finally, the purified hydrogels showed cytocompatibility and enabled cell adhesion of human umbilical artery smooth muscle cells (HUASMCs) after direct seeding. The materials further allowed the adhesion and growth of an endothelial layer, triggered no pro-inflammatory response as evidenced by cytokine release of M0 macrophages, and exhibited antibacterial properties toward S. aureus and E. coli.

Solid-State Nanopore-Based Nanosystem for Registration of Enzymatic Activity of a Single Molecule of Cytochrome P450 BM3.

Experimental methods of single-molecule enzymology allow scientists to determine physicochemical properties of distinct single molecules of various enzymes and to perform direct monitoring of functioning of enzymes at different steps of their catalytic cycle. The approach based on the use of solid-state nanopores is a promising tool for studying the functioning of single-enzyme molecules. Herein, this approach is employed for monitoring the functioning of cytochrome P450 BM3, which represents a very convenient model of cytochrome P450-containing monooxygenase systems. A nanopore of ~5 nm in diameter has been formed in a 40 nm-thick silicon nitride chip by electron beam drilling (EBD), and a single molecule of the BM3 enzyme has been entrapped in the pore. The functioning of the enzyme molecule has been monitored by recording the time dependence of the ion current through the nanopore during the reaction of laurate hydroxylation. In our experiments, the enzyme molecule has been found to be active for 1500 s. The results of our research can be further used in the development of highly sensitive detectors for single-molecule studies in enzymology.

Predicting standardized uptake value of brown adipose tissue from CT scans using convolutional neural networks.

The standard method for identifying active Brown Adipose Tissue (BAT) is [18F]-Fluorodeoxyglucose ([18F]-FDG) PET/CT imaging, which is costly and exposes patients to radiation, making it impractical for population studies. These issues can be addressed with computational methods that predict [18F]-FDG uptake by BAT from CT; earlier population studies pave the way for developing such methods by showing some correlation between the Hounsfield Unit (HU) of BAT in CT and the corresponding [18F]-FDG uptake in PET. In this study, we propose training convolutional neural networks (CNNs) to predict [18F]-FDG uptake by BAT from unenhanced CT scans in the restricted regions that are likely to contain BAT. Using the Attention U-Net architecture, we perform experiments on datasets from four different cohorts, the largest study to date. We segment BAT regions using predicted [18F]-FDG uptake values, achieving 23% to 40% better accuracy than conventional CT thresholding. Additionally, BAT volumes computed from the segmentations distinguish the subjects with and without active BAT with an AUC of 0.8, compared to 0.6 for CT thresholding. These findings suggest CNNs can facilitate large-scale imaging studies more efficiently and cost-effectively using only CT.

Phosphine selenides: versatile NMR probes for analyzing hydrogen OH⋯Se and halogen I⋯Se bonds.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for studying the structure and dynamics of various non-covalent interactions. However, often spectral parameters that are applicable for estimation of parameters of one type of non-covalent interaction will be inapplicable for another. Therefore, researchers are compelled to use spectral parameters that are specifically tailored to the type of non-covalent interaction being studied. This complexity makes it difficult to compare different types of non-covalent interactions with each other and, consequently, to establish a strict unified classification for them. This pioneering study proposes to use phosphine selenides as universal probes for investigating hydrogen and halogen bonding in solution. The study was carried out using the example of triethylphosphine selenide Et3PSe complexes with hydrogen bonds of Se⋯HO type and R3PSe (where R: Me, Et, n-Bu, t-Bu and Ph) with halogen bonds of Se⋯X type (where X: I and Br) in solution. The presence of non-covalent interactions was confirmed experimentally by means of 1H, 31P and 77Se NMR, as well as by quantum chemical calculation methods (optimization: PW6B95-D3/def2-QZVP; NMR: B97-2/pcsSeg-2).

Brain-Derived Neurotrophic Factor (BDNF) in the Frontal Cortex Enhances Social Interest in the BTBR Mouse Model of Autism.

A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals.

Thermosensitive injectable fibrillar gels based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) as biocompatible brain implants.

Drug treatment of glioblastoma, the most aggressive and widespread form of brain cancer, is complicated due to the difficulty of penetration of chemotherapeutic drugs through the blood-brain barrier (BBB). Moreover, with surgical removal of tumors, in 90 % of cases they reappear near the original focus. To solve this problem, we propose to use hydrogel based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) (CNC-g-PNIPAM) as a promising material for filling postoperative cavities in the brain with the release of antitumor drugs. The CNC-g-PNIPAM is formed by "grafting to" method for precise control of molecular weight and grafting density. This colloidal system is liquid under injection conditions (at r. t.) and turns into a gel at human body temperature (when filling the postoperative area). It was shown for the first time that due to the rod-shaped of CNC, the gel has a fibrillar structure and, thus, mechanical properties similar to those of brain tissue, including nonlinear mechanics (strain-stiffening and compression softening). The biocompatibility of the hydrogel with primary brain cells is demonstrated. In addition, the release of the antitumor drug paclitaxel from the hydrogel and its antitumor activity is shown. The resulting nanocolloid system provides an innovative alternative approach to filling postoperative cavities and can be used for postoperative treatment due to the programmable release of drugs, as well as for in vitro modeling of tumor interaction with the BBB affecting drug transport in the brain.

RiboVision2: A Web Server for Advanced Visualization of Ribosomal RNAs.

RiboVision2 is a web server designed to visualize phylogenetic, structural, and evolutionary properties of ribosomal RNAs simultaneously at the levels of primary, secondary, and three-dimensional structure and in the context of full ribosomal complexes. RiboVision2 instantly computes and displays a broad variety of data; it has no login requirements, is open-source, free for all users, and available at https://ribovision2.chemistry.gatech.edu.

Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma.

BACKGROUND: Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS: In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS: 23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT: This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

Enabling Visible Light Sensitization of YbIII, NdIII and ErIII in Dimeric LnIII/GaIII Metallacrowns through Functionalization with RuII Complexes for NIR-II Multiplex Imaging.

Multiplex imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides exciting opportunities for more precise understanding of biological processes and more accurate diagnosis of diseases by enabling real-time acquisition of images with improved contrast and spatial resolution in deeper tissues. Today, the number of imaging agents suitable for this modality remains very scarce. In this work, we have synthesized and fully characterized, including theoretical calculations, a series of dimeric LnIII/GaIII metallacrowns bearing RuII polypyridyl complexes, LnRu-3 (Ln = YIII, YbIII, NdIII, ErIII). Relaxed structures of YRu-3 in the ground and the excited electronic states have been calculated using dispersion-corrected density functional theory methods. Detailed photophysical studies of LnRu-3 have demonstrated that characteristic emission signals of YbIII, NdIII and ErIII in the NIR-II range can be sensitized upon excitation in the visible range through RuII-centered metal-to-ligand charge transfer (MLCT) states. We have also showed that these NIR-II signals are unambiguously detected in an imaging experiment using capillaries and biological tissue-mimicking phantoms. This work opens unprecedented perspectives for NIR-II multiplex imaging using LnIII-based molecular compounds.

Molecular Insights into Adhesion at Interface of Geopolymer Binder and Cement Mortar.

The degradation of concrete and reinforced concrete structures is a significant technical and economic challenge, requiring continuous repair and rehabilitation throughout their service life. Geopolymers (GPs), known for their high mechanical strength, low shrinkage, and durability, are being increasingly considered as alternatives to traditional repair materials. However, there is currently a lack of understanding regarding the interface bond properties between new geopolymer layers and old concrete substrates. In this paper, using advanced computational techniques, including quantum mechanical calculations and stochastic modeling, we explored the adsorption behavior and interaction mechanism of aluminosilicate oligomers with different Si/Al ratios forming the geopolymer gel structure and calcium silicate hydrate as the substrate at the interface bond region. We analyzed the electron density distributions of the highest occupied and lowest unoccupied molecular orbitals, examined the reactivity indices based on electron density functional theory, performed Mulliken charge population analysis, and evaluated global reactivity descriptors for the considered oligomers. The results elucidate the mechanisms of local and global reactivity of the oligomers, the equilibrium low-energy configurations of the oligomer structures adsorbed on the surface of C-(A)-S-H(I) (100), and their adsorption energies. These findings contribute to a better understanding of the adhesion properties of geopolymers and their potential as effective repair materials.

The "Hungry Judge" effect on prostate MRI reporting: Chronobiological trends from 35'004 radiologist interpretations.

AIM: To investigate the associations between the hour of the day and Prostate Imaging-Reporting and Data System (PI-RADS) scores assigned by radiologists in prostate MRI reports. MATERIALS AND METHODS: Retrospective single-center collection of prostate MRI reports over an 8-year period. Mean PI-RADS scores assigned between 0800 and 1800 h were examined with a regression model. RESULTS: A total of 35'004 prostate MRI interpretations by 26 radiologists were included. A significant association between the hour of day and mean PI-RADS score was identified (ß2 = 0.005, p < 0.001), with malignant scores more frequently assigned later in the day. CONCLUSION: These findings suggest chronobiological factors may contribute to variability in radiological assessments. Though the magnitude of the effect is small, this may potentially add variability and impact diagnostic accuracy.

Content, educational value and quality analysis of videos about neurorehabilitation in people with multiple sclerosis on YouTube®. / Análisis de contenido, valor educativo y calidad de los vídeos sobre neurorrehabilitación de la esclerosis múltiple en YouTube®.

INTRODUCTION: The use of YouTube® has spread among patients with chronic diseases such as multiple sclerosis (MS). These patients consult the available videos to learn more about their disease in terms of diagnosis and making decisions about treatments, including rehabilitation. The aim of this study was to evaluate the content, educational value, and quality analysis of MS videos about neurorehabilitation on YouTube® using quantitative instruments. MATERIALS AND METHODS: A search was conducted on YouTube®. The first 30 videos that met the inclusion criteria were reviewed. The videos were classified according to the upload source and the content. All videos included in the review were assessed by the DISCERN questionnaire, the JAMA benchmark, the global quality scale (GQS) and the video information and quality index (VIQI). RESULTS: The mean scores were: 28.3 (±9.33) in DISCERN, 2 (±0.81) in JAMA, 2.57 (±1.22) in GQS, and 11.73 (±4.06) in VIQI. JAMA score statistically significantly differed according to upload source (p = 0.002), video content (p = 0.023) and the speaker (p = 0.002). The DISCERN, JAMA, GQS, and VIQI scores showed significant correlations with each other. CONCLUSIONS: The analyzed videos about neurorehabilitation in people with MS on YouTube® were quite old since the upload, with a moderate duration and number of views, but with a poor quality of the content, educational value, and quality analysis of the videos. Our research showed that there were statistically significant differences in terms of quality, transparency, and reliability of the information, depending on the upload source, video content and the speaker.

TITLE: Análisis de contenido, valor educativo y calidad de los vídeos sobre neurorrehabilitación de la esclerosis múltiple en YouTube®.Introducción. El uso de YouTube® se ha extendido entre los pacientes con enfermedades crónicas como la esclerosis múltiple (EM). Estos pacientes tienden a consultar los vídeos disponibles para aprender más sobre su enfermedad, en términos de diagnóstico y toma de decisiones sobre tratamientos, incluida la rehabilitación. El objetivo de este estudio fue evaluar el contenido, el valor educativo y el análisis de la calidad de los vídeos sobre neurorrehabilitación de la EM en la plataforma YouTube®, empleando instrumentos cuantitativos validados. Materiales y métodos. Se realizó una búsqueda en la plataforma YouTube®. Se revisaron los 30 primeros vídeos que cumplían los criterios de inclusión establecidos. Los vídeos se clasificaron según la fuente de subida y el contenido. Todos los vídeos incluidos en la revisión se evaluaron mediante el cuestionario DISCERN, el índice de referencia JAMA, la escala de calidad global (GQS) y el índice de información y calidad de vídeo (VIQI). Resultados. Las puntuaciones medias fueron: 28,3 (±9,33) en DISCERN, 2 (±0,81) en JAMA, 2,57 (±1,22) en GQS y 11,73 (±4,06) en VIQI. La puntuación en la escala JAMA difirió de forma estadísticamente significativa según la fuente de carga (p = 0,002), el contenido del vídeo (p = 0,023) y el perfil de la persona que lo ejecutaba (p = 0,002). Las puntuaciones en DISCERN, JAMA, GQS y VIQI mostraron correlaciones significativas entre sí. Conclusiones. Los vídeos analizados sobre neurorrehabilitación en personas con EM y que aparecen en la plataforma YouTube® eran bastante antiguos desde su fecha de subida, con una duración y un número de visualizaciones moderados, y con una calidad deficiente en su contenido, en su valor educativo y en el propio análisis de los mismos. Nuestra investigación mostró que había diferencias estadísticamente significativas en términos de calidad, transparencia y fiabilidad de la información, dependiendo de la fuente de subida, el contenido del vídeo y el perfil de la persona que lo ejecutaba.

Mono- and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules.

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

Preparation of Langmuir-Blodgett Films from Quinoxalines Exhibiting Aggregation-Induced Emission and Their Acidochromism.

The development of aggregation-induced emission (AIE)-exhibiting compounds heavily relies on our evolving comprehension of their behavior at interfaces, an understanding that still remains notably limited. In this study, we explored the preparation of two-dimensional (2D) sensing films from 2,3-diphenylquinoxaline-based diazapolyoxa- and polyazamacrocycles displaying AIE via the Langmuir-Blodgett (LB) technique. This systematic investigation highlights the key role of the heteroatom-containing tether of 2,3-diphenylquinoxalines in the successful fabrication of Langmuir layers at the air-water interface and the transfer of AIE-emitting supramolecular aggregates onto solid supports. Using both diazapolyoxa- and polyazamacrocycles, we prepared AIE-exhibiting monolayer films containing emissive supramolecular aggregates on silica, mica, and quartz glass and characterized them using ultraviolet-visible (UV-vis) and photoluminescence (PL) spectroscopies, atomic force microscopy (AFM) imaging, and fluorescence microscopy. We also obtained multilayer AIE-emitting films through the LB technique, albeit with increased complexity. Remarkably, by employing the smallest macrocycle N2C3Q, we successfully prepared LB films suitable for the visual detection of acidic vapors. This sensing material, which contains a much lesser amount of organic dye compared with traditional drop-cast films, can be regenerated and utilized for real-life sample analysis, such as monitoring the presence of ammonia in the air and the freshness of meat.

Unveiling the electronic structure peculiarities of phosphine selenides as NMR probes for non-covalent interactions: an experimental and theoretical study.

In this work, R3PSe (R = Me, Et, n-Bu, t-Bu and Ph) were studied experimentally using NMR spectroscopy in solution and the solid-state in combinaton with quantum chemical methods. The study shows that the NMR parameters of these phosphine selenides, such as δP, δSe, and 1JPSe, are sensitive to subtle changes in the electronic environment of the P and Se atoms. Consequently, phosphine selenides R3PSe can serve as promising spectral probes for the detection and quantitative investigation of various non-covalent interactions. Additionally, the variations of R in phosphine selenides influence the observed NMR spectral parameters, primarily through effects such as π-backdonation and hyperconjugation, which have been observed experimentally and confirmed theoretically.

Inguinal lymph node metastases from prostate cancer: clinical, pathology, and multimodality imaging considerations.

Objective: To investigate clinical, pathology, and imaging findings associated with inguinal lymph node (LN) metastases in patients with prostate cancer (PCa). Materials and Methods: This was a retrospective single-center study of patients with PCa who underwent imaging and inguinal LN biopsy between 2000 and 2023. We assessed the following aspects on multimodality imaging: inguinal LN morphology; extrainguinal lymphadenopathy; the extent of primary and recurrent tumors; and non-nodal metastases. Imaging, clinical, and pathology features were compared between patients with and without metastatic inguinal LNs. Results: We evaluated 79 patients, of whom 38 (48.1%) had pathology-proven inguinal LN metastasis. Certain imaging aspects- short-axis diameter, prostate-specific membrane antigen uptake on positron-emission tomography, membranous urethra involvement by the tumor, extra-inguinal lymphadenopathy, and distant metastases-were associated with pathology-proven inguinal LN metastases (p < 0.01 for all). Associations with long-axis diameter, fatty hilum, laterality, and uptake of other tracers on positronemission tomography were not significant (p = 0.09-1.00). The patients with metastatic inguinal LNs had higher prostate-specific antigen levels and more commonly had castration-resistant PCa (p < 0.01), whereas age, histological grade, and treatment type were not significant factors (p = 0.07-0.37). None of the patients had inguinal LN metastasis in the absence of locally advanced disease with membranous urethra involvement or distant metastasis. Conclusion: Several imaging, clinical, and pathology features are associated with inguinal LN metastases in patients with PCa. Isolated metastasis to inguinal LNs is extremely rare and unlikely to occur in the absence of high-risk imaging, clinical, or pathology features.

Objetivo: Investigar achados clinicopatológicos e de imagem associados a metástases linfonodais inguinais em pacientes com câncer de próstata (CaP). Materiais e Métodos: Estudo retrospectivo de uma única instituição de pacientes com CaP submetidos a exames de imagem e biópsia inguinal de linfonodos em 2000­2023. A imagem multimodalidade foi avaliada para morfologia inguinal do linfonodo, linfadenopatia fora da região inguinal, extensão do CaP primário/recorrente e sítios metastáticos não nodais. Características de imagem e clinicopatológicas foram comparadas entre pacientes com e sem linfonodos inguinais metastáticos pela patologia. Resultados: Entre 79 pacientes estudados, 38 (48,1%) apresentaram metástase inguinal de linfonodo comprovada patologicamente. Certos achados de imagem ­ diâmetro do eixo curto, captação do antígeno de membrana prostático específico na tomografia por emissão de pósitrons, envolvimento da uretra membranosa pelo tumor, linfadenopatia fora da região inguinal e metástases a distância ­ foram associados com metástases inguinais no linfonodo pela patologia (p < 0,01). Diâmetro de eixo longo, hilo gorduroso, lateralidade, captação em outros traçadores de tomografia por emissão de pósitrons não foram significativos (p = 0,09­1,00). Clinicopatologicamente, os pacientes com linfonodos inguinais metastáticos apresentaram maior antígeno prostático específico e foram mais resistentes à castração (p < 0,01); idade, grau histológico e tipo de tratamento não foram estatisticamente significantes (p = 0,07­0,37). Nenhum paciente apresentou metástase inguinal isolada no linfonodo na ausência de doença localmente avançada com envolvimento da uretra membranosa ou metástase a distância. Conclusão: Várias características de imagem e clinicopatológicas foram associadas a metástases em LNs inguinais em pacientes com CaP. A metástase isolada para os LNs inguinais é extremamente rara e é improvável que ocorra na ausência de características de imagem e clinicopatológicas de alto risco.

Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial.

Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2-menaquinone-7 (MK-7)-or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.

Unique Role of Vimentin in the Intermediate Filament Proteins Family.

Intermediate filaments (IFs), being traditionally the least studied component of the cytoskeleton, have begun to receive more attention in recent years. IFs are found in different cell types and are specific to them. Accumulated data have shifted the paradigm about the role of IFs as structures that merely provide mechanical strength to the cell. In addition to this role, IFs have been shown to participate in maintaining cell shape and strengthening cell adhesion. The data have also been obtained that point out to the role of IFs in a number of other biological processes, including organization of microtubules and microfilaments, regulation of nuclear structure and activity, cell cycle control, and regulation of signal transduction pathways. They are also actively involved in the regulation of several aspects of intracellular transport. Among the intermediate filament proteins, vimentin is of particular interest for researchers. Vimentin has been shown to be associated with a range of diseases, including cancer, cataracts, Crohn's disease, rheumatoid arthritis, and HIV. In this review, we focus almost exclusively on vimentin and the currently known functions of vimentin intermediate filaments (VIFs). This is due to the structural features of vimentin, biological functions of its domains, and its involvement in the regulation of a wide range of basic cellular functions, and its role in the development of human diseases. Particular attention in the review will be paid to comparing the role of VIFs with the role of intermediate filaments consisting of other proteins in cell physiology.