Interferon-gamma signaling drives epithelial TNF-alpha receptor-2 expression during colonic tissue repair.

Interferon-gamma (IFNγ) is traditionally recognized for its pro-inflammatory role during intestinal inflammation. Here, we demonstrate that IFNγ also functions as a pro-repair molecule by increasing TNFα receptor 2 (TNFR2 protein/TNFRSF1B gene) expression on intestinal epithelial cells (IEC) following injury in vitro and in vivo. In silico analyses identified binding sites for the IFNγ signaling transcription factor STAT1 in the promoter region of TNFRSF1B. Scratch-wounded IEC exposed to IFNγ exhibited a STAT1-dependent increase in TNFR2 expression. In situ hybridization revealed elevated Tnfrsf1b mRNA levels in biopsy-induced colonic mucosal wounds, while intraperitoneal administration of IFNγ neutralizing antibodies following mucosal injury resulted in impaired IEC Tnfrsf1b mRNA and inhibited colonic mucosal repair. These findings challenge conventional notions that "pro-inflammatory" mediators solely exacerbate damage by highlighting latent pro-repair functions. Moreover, these results emphasize the critical importance of timing and amount in the synthesis and release of IFNγ and TNFα during the inflammatory process, as they are pivotal in restoring tissue homeostasis.

Utility index and vision-related quality of life in patients awaiting specialist eye care.

OBJECTIVES: This study aimed to ascertain utility and vision-related quality of life in patients awaiting access to specialist eye care. A secondary aim was to evaluate the association of utility indices with demographic profile and waiting time. METHODS: Consecutive patients that had been waiting for ophthalmology care answered the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The questionnaire was administered when patients arrived at the clinics for their first visit. We derived a utility index (VFQ-UI) from the patients' responses, then calculated the correlation between this index and waiting time and compared utility across demographic subgroups stratified by age, sex, and care setting. RESULTS: 536 individuals participated in the study (mean age 52.9±16.6 years; 370 women, 69% women). The median utility index was 0.85 (interquartile range [IQR] 0.70-0.92; minimum 0.40, maximum 0.97). The mean VFQ-25 score was 70.88±14.59. Utility correlated weakly and nonsignificantly with waiting time (-0.05, P = 0.24). It did not vary across age groups (P = 0.85) or care settings (P = 0.77). Utility was significantly lower for women (0.84, IQR 0.70-0.92) than men (0.87, IQR 0.73-0.93, P = 0.03), but the magnitude of this difference was small (Cohen's d = 0.13). CONCLUSION: Patients awaiting access to ophthalmology care had a utility index of 0.85 on a scale of 0 to 1. This measurement was not previously reported in the literature. Utility measures can provide insight into patients' perspectives and support economic health analyses and inform health policies.

Synthesis and Superficial Modification "In Situ" of Copper Selenide (Cu2-x Se) Nanoparticles and Their Antibacterial Activity.

Copper selenide nanoparticles (Cu2-x Se NPs) have received a lot of attention in recent decades due to their interesting properties and potential applications in various areas such as electronics, health, solar cells, etc. In this study, details of the synthesis and characterization of copper selenide nanoparticles modified with gum arabic (GA) are reported. Also, through transmission electronic microscopy (TEM) analysis, the transformation of the morphology and particle size of copper selenide nanoparticles in aqueous solution was studied. In addition, we present an antimicrobial study with different microorganisms such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Candida albiacans (C. albicans). Copper selenide nanoparticles were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry analysis (DSC) and TEM. XRD confirmed the crystal-line structure of the nanoparticles such as cubic berzelanite with a particle size of 6 nm ± 0.5. FTIR and TGA corroborated the surface modification of copper selenide nanoparticles with gum arabic, and DSC suggested a change in the structural phase from cubic to hexagonal. TEM analysis demonstrated that the surface modification of the Cu2-x Se NPs stabilized the nanostructure of the particles, preventing changes in the morphology and particle size. The antimicrobial susceptibility analysis of copper selenide nanoparticles indicated that they have the ability to inhibit the microbial growth of Staphylococcus aureus, Escherichia coli and Candida albicans.

Doubts about the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth service.

This cross-sectional study aims to describe doubts regarding the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth service. All teleconsultations (TCs) offered through TelessaúdeRS-UFRGS to primary health care (PHC) services in the state of Rio Grande do Sul between 2018 and 2021 involving syphilis in pregnancy were included. A total of 356 (TCs) were analyzed. The main doubts about syphilis during pregnancy raised by primary care professionals were related to the need for retreatment (35%), diagnostic definition (23%) and initial treatment (16%). In addition, 95% of TCs were suitable for diagnosing and treating syphilis based on the 2020 Brazilian Ministry of Health guideline. This study suggests that TCs can identify failures in the diagnosis and treatment of public health problems and support decision making in PHC involving syphilis in pregnancy.

Idiopathic fibrosing pancreatitis: A rare cause of obstructive jaundice.

Jaundice is an important physiologic manifestation of both benign and insidious diseases. We report on the case of an 11-year-old male who presented with diffuse pruritis, jaundice, and later abdominal pain. Initial work-up revealed an obstructive cholestatic pattern, warranting investigation for structural anomalies. Extensive imaging revealed a lesion on the pancreatic head, and biopsy of the lesion confirmed the diagnosis of idiopathic fibrosing pancreatitis (IFP). Temporary stenting of the common bile duct successfully treated our patient's symptomatic IFP.

Co3O4/activated carbon nanocomposites as electrocatalysts for the oxygen evolution reaction.

The Oxygen Evolution Reaction (OER) is crucial in various processes such as hydrogen production via water splitting. Several electrocatalysts, including metal oxides, have been evaluated to enhance the reaction efficiency. Zeolitic Imidazolate Framework-67 (ZIF-67) has been employed as a precursor to produce Co3O4, showing high OER activity. Additionally, the formation of composites with carbon-based materials improves the activity of these materials. Thus, this work focuses on synthesizing ZIF-67 and commercial activated carbon (AC) composites, which were used as precursors to obtain Co3O4/C electrocatalysts by calculating ZIF-67/CX (X = 10, 30, and 50, the mass percentage of AC). The obtained materials were thoroughly characterized by employing X-ray powder diffraction (XRD), confirming the cobalt oxide structure with a sphere-like morphology as observed in the TEM images. The presence of oxygen vacancies was confirmed by infrared spectroscopy and EPR measurements. The electrocatalytic performance in the OER was investigated by linear sweep voltammetry (LSV), which revealed an overpotential of 325 mV at 10 mA cm-2 and a Tafel slope value of 65.32 mV dec-1 for Co3O4/C10, superior in activity to several previously reported studies in the literature and electrochemical stability of up to 8 hours. The reduced value of charge transfer resistance, high double-layer capacitance, and the presence of Co3+ ions justify the superior performance of the Co3O4/C10 electrocatalyst.

Rosuvastatin effect on atherosclerotic plaque metabolism: A subclinical atherosclerosis imaging study with 18F-NaF PET-CT.

BACKGROUND AND AIMS: Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. METHODS: Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. RESULTS: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL-1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003). CONCLUSION: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.

DrugBank 6.0: the DrugBank Knowledgebase for 2024.

First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.

Incremento na prática de exercícios físicos ao ar livre após o início da pandemia covid-19 entre acadêmicos de medicina / Increase in the practice of outdoor physical exercises after the beginning of the pandemic among medicine students

Introdução: A atividade física é uma ferramenta importante para a manutenção e promoção da saúde física e mental, porém, diante da pandemia instalada mundialmente pelo coronavírus e consequentemente o distanciamento social para o controle de sua disseminação, foram necessárias adaptações na prática de exercícios físicos, como sua maior realização em ambientes abertos. Objetivo: Investigar se houve incremento na prática de exercícios físicos ao ar livre após o início da pandemia entre acadêmicos de Medicina de uma faculdade do noroeste paulista. Método: Trata-se de estudo transversal descritivo, com abordagem quantitativa dos dados, realizado através de um questionário on-line. Resultados: No total, 189 estudantes participaram da pesquisa. Os resultados indicaram que 74,60% dos participantes afirmaram que se exercitaram ao ar livre neste período, sendo que 29,63% não tinham esse hábito anteriormente, além disso, a frequência dessas atividades aumentou, já que durante a pandemia, 41% dos estudantes relataram se exercitar quatro ou mais vezes por semana ao ar livre, enquanto anteriormente essa proporção era de 22,75%, sendo a principal motivação, a preocupação com a saúde mental (60,67%). Conclusão: Foram identificadas mudanças na prática de exercício físico pelos estudantes de medicina, através da realização desta ao ar livre e com aumento de sua periodicidade

Introduction: Physical activity is an important tool for maintaining and promoting physical and mental health, however, in view of the pandemic installed worldwide by the coronavirus and consequently social distancing to control its spread, adaptations were necessary in the practice of physical exercises, as his greatest achievement in open environments. Objective: To investigate whether there was an increase in outdoor physical exercise after the start of the pandemic among medical students at a college in the northwest of São Paulo. Method: This is a descriptive cross-sectional study, with a quantitative approach to the data, carried out through an online questionnaire. Results: In total, 189 students participated in the survey. The results indicated that 74.60% of the participants stated that they exercised outdoors during this period, with 29.63% not having this habit before, in addition, the frequency of these activities increased, since during the pandemic, 41% of students reported exercising four or more times a week outdoors, while previously this proportion was 22.75%, the main motivation being concern for mental health (60.67%). Conclusion: Changes were identified in the practice of physical exercise by medical students, by performing it outdoors and with increased frequency

Introducción: La actividad física es una herramienta importante para el mantenimiento y promoción de la salud física y mental, sin embargo, ante la pandemia instalada a nivel mundial por el coronavirus y consecuentemente el distanciamiento social para controlar su propagación, fueron necesarias adaptaciones en la práctica de ejercicios físicos, como su mayor logro en ambientes abiertos. Objetivo: Investigar si hubo un aumento del ejercicio físico al aire libre después del inicio de la pandemia entre los estudiantes de medicina de una facultad del noroeste de São Paulo. Método: Se trata de un estudio descriptivo transversal, con abordaje cuantitativo de los datos, realizado a través de un cuestionario online. Resultados: En total, 189 estudiantes participaron en la encuesta. Los resultados indicaron que el 74,60% de los participantes manifestaron realizar ejercicio al aire libre durante este período, siendo que el 29,63% no tenían este hábito antes, además, aumentó la frecuencia de estas actividades, ya que durante la pandemia, el 41% de los estudiantes reportaron realizar ejercicio de cuatro o más veces a la semana al aire libre, mientras que antes esta proporción era del 22,75%, siendo la principal motivación la preocupación por la salud mental (60,67%). Conclusión: Se identificaron cambios en la práctica de ejercicio físico de los estudiantes de medicina, al realizarlo al aire libre y con mayor frecuencia

New paleopathological findings from the Quaternary of the Brazilian Intertropical Region expand the distribution of joint diseases for the South American megafauna.

OBJECTIVE: To evaluate pathological changes in fossils from the Brazilian Intertropical Region (BIR), expanding the records of previously reported diseases for representatives of the Quaternary South American megafauna, including taxa not studied in previous works. MATERIALS AND METHODS: We carried out a thorough macroscopic analysis of fifteen unpublished specimens belonging to representatives of the Quaternary megafauna of BIR to identify evidence of pathological alterations. RESULTS: Alterations included: osteophytes in Toxodontidae, Megatheridae and E. laurillardi; rough subchondral bone, bone overgrowth and bone erosion in E. laurillardi; slit-shaped subchondral depressions in Equidae and E. laurillardi; and a triangular-shaped porous lesion in Mylodontidae. CONCLUSIONS: The alterations found allowed the recognition of the first cases of osteoarthritis for Toxodontidae and articular depressions for Equidae, and new cases of both diseases in Eremotherium laurillardi; a new case of osteochondritis dissecans for Mylodontidae; potential new cases of calcium pyrophosphate deposition and spondyloarthropathy for E. laurillardi SIGNIFICANCE: Our results provide additional evidence that calcium pyrophosphate deposition disease was widely spread among species of the South American megafauna and suggest that osteochondritis dissecans may have been relatively common among ground sloths. LIMITATIONS: The identification of calcium pyrophosphate deposition and spondyloarthropathy in E. laurillardi are quite tentative because the evidence found is ambiguous and the number of examined specimens is limited.

Does vegetation accelerate coastal dune erosion during extreme events?

A broadly accepted paradigm is that vegetation reduces coastal dune erosion. However, we show that during an extreme storm event, vegetation surprisingly accelerates erosion. In 104-m-long beach-dune profile experiments conducted within a flume, we discovered that while vegetation initially creates a physical barrier to wave energy, it also (i) decreases wave run-up, which creates discontinuities in erosion and accretion patterns across the dune slope, (ii) increases water penetration into the sediment bed, which induces its fluidization and destabilization, and (iii) reflects wave energy, accelerating scarp formation. Once a discontinuous scarp forms, the erosion accelerates further. These findings fundamentally alter the current understanding of how natural and vegetated features may provide protection during extreme events.

Sargassum natans I Algae: An Alternative for a Greener Approach for the Synthesis of ZnO Nanostructures with Biological and Environmental Applications.

In this work, the influence of the Sargassum natans I alga extract on the morphological characteristics of synthesized ZnO nanostructures, with potential biological and environmental applications, was evaluated. For this purpose, different ZnO geometries were synthesized by the co-precipitation method, using Sargassum natans I alga extract as stabilizing agent. Four extract volumes (5, 10, 20, and 50 mL) were evaluated to obtain the different nanostructures. Moreover, a sample by chemical synthesis, without the addition of extract, was prepared. The characterization of the ZnO samples was carried out by UV-Vis spectroscopy, FT-IR spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that the Sargassum alga extract has a fundamental role in the stabilization process of the ZnO nanoparticles. In addition, it was shown that the increase in the Sargassum alga extract leads to preferential growth and arrangement, obtaining well-defined shaped particles. ZnO nanostructures demonstrated significant anti-inflammatory response by the in vitro egg albumin protein denaturation for biological purposes. Additionally, quantitative antibacterial analysis (AA) showed that the ZnO nanostructures synthesized with 10 and 20 mL of extract demonstrated high AA against Gram (+) S. aureus and moderate AA behavior against Gram (-) P. aeruginosa, depending on the ZnO arrangement induced by the Sargassum natans I alga extract and the nanoparticles' concentration (ca. 3200 µg/mL). Additionally, ZnO samples were evaluated as photocatalytic materials through the degradation of organic dyes. Complete degradation of both methyl violet and malachite green were achieved using the ZnO sample synthesized with 50 mL of extract. In all cases, the well-defined morphology of ZnO induced by the Sargassum natans I alga extract played a key role in the combined biological/environmental performance.

Electrochemical Deposition of Polypyrrole in the Presence of Silanes as Adhesion Promoters.

Polypyrrole adhesion to indium-tin oxide electrodes was improved by adding pre-hydrolyzed alkoxysilanes to the electrodeposition media. The pyrrole oxidation and film growth rates were studied by potentiostatic polymerization in acidic media. The morphology and thickness of the films were studied by contact profilometry and surface-scanning electron microscopy. The bulk and surface semiquantitative chemical composition was studied by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Finally, the adhesion was studied by scotch-tape adhesion test, where both alkoxysilanes showed a significant improvement in adhesion. We proposed a hypothesis for the improvement in adhesion, that involves the formation of siloxane material as well as in situ surface modification of the transparent metal oxide electrode.

Gut Bacterial Communities in HIV-Infected Individuals with Metabolic Syndrome: Effects of the Therapy with Integrase Strand Transfer Inhibitor-Based and Protease Inhibitor-Based Regimens.

Antiretroviral therapies (ART) are strongly associated with weight gain and metabolic syndrome (MetS) development in HIV-infected patients. Few studies have evaluated the association between gut microbiota and integrase strand transfer inhibitor (INSTI)-based and protease inhibitor (PI)-based regimens in HIV-infected patients with MetS. To assess this, fecal samples were obtained from HIV-infected patients treated with different regimens (16 PI + MetS or 30 INSTI + MetS) and 18 healthy controls (HCs). The microbial composition was characterized using 16S rRNA amplicon sequencing. The INSTI-based and PI-based regimens were associated with a significant decrease in α-diversity compared to HCs. The INSTI + MetS group showed the lowest α-diversity between both regimens. A significant increase in the abundance of short-chain fatty acid (SCFA)-producing genera (Roseburia, Dorea, Ruminococcus torques, and Coprococcus) was observed in the PI + MetS group, while Prevotella, Fusobacterium, and Succinivibrio were significantly increased in the INSTI + MetS group. Moreover, the Proteobacteria/Firmicutes ratio was overrepresented, and functional pathways related to the biosynthesis of LPS components were increased in the INSTI + MetS group. The gut microbiota of patients receiving INSTIs showed a more pronounced dysbiosis orchestrated by decreased bacterial richness and diversity, with an almost complete absence of SCFA-producing bacteria and alterations in gut microbiota functional pathways. These findings have not been previously observed.

Effect of antiretroviral therapy on decreasing arterial stiffness, metabolic profile, vascular and systemic inflammatory cytokines in treatment-naïve HIV: A one-year prospective study.

INTRODUCTION: Cardiovascular disease is a major cause of death among people living with HIV (PLH). Non-treated PLH show increased levels of inflammation and biomarkers of vascular activation, and arterial stiffness as a prognostic cardiovascular disease risk factor. We investigated the effect of one year of ART on treatment-naïve HIV(+) individuals on arterial stiffness and inflammatory and vascular cytokines. METHODS: We cross-sectionally compared aortic stiffness via tonometry, inflammatory, and vascular serum cytokines on treatment-naïve (n = 20) and HIV (-) (n = 9) matched by age, sex, metabolic profile, and Framingham score. We subsequently followed young, treatment-naïve individuals after 1-year of ART and compared aortic stiffness, metabolic profile, and inflammatory and vascular serum biomarkers to baseline. Inflammatory biomarkers included: hs-CRP, D-Dimer, SAA, sCD163s, MCP-1, IL-8, IL-18, MRP8/14. Vascular cytokines included: myoglobin, NGAL, MPO, Cystatin C, ICAM-1, VCAM-1, and MMP9. RESULTS: Treatment-naïve individuals were 34.8 years old, mostly males (95%), and with high smoking prevalence (70%). Baseline T CD4+ was 512±324 cells/mcL. cfPWV was similar between HIV(-) and treatment-naïve (6.8 vs 7.3 m/s; p = 0.16) but significantly decreased after ART (-0.52 m/s; 95% CI -0.87 to -0.16; p0.006). Almost all the determined cytokines were significantly higher compared to controls, except for MCP-1, myoglobin, NGAL, cystatin C, and MMP-9. At follow-up, only total cholesterol and triglycerides increased and all inflammatory cytokines significantly decreased. Regarding vascular cytokines, MPO, ICAM-1, and VCAM-1 showed a reduction. D-Dimer tended to decrease (p = 0.06) and hs-CRP did not show a significant reduction (p = 0.17). CONCLUSION: One year of ART had a positive effect on reducing inflammatory and vascular cytokines and arterial stiffness.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Antibacterial and Anti-Inflammatory Properties of ZnO Nanoparticles Synthesized by a Green Method Using Sargassum Extracts.

The present work shows the synthesis of ZnO nanoparticles through a green method, using sargassum extracts, which provide the reducing and stabilizing compounds. The conditions of the medium in which the reaction was carried out was evaluated, that is, magnetic stirring, ultrasound assisted, and resting condition. UV-Vis, FTIR spectroscopy, and X-ray diffraction results confirmed the synthesis of ZnO with nanometric crystal size. The scanning electron microscopy analysis showed that the morphology and size of the particles depends on the synthesis condition used. It obtained particles between 20 and 200 nm in the sample without agitation, while the samples with stirring and ultrasound were 80 nm and 100 nm, respectively. ZnO nanoparticles showed antibacterial activity against Gram-positive S. aureus and Gram-negative P. aeruginosa. A quantitative analysis was performed by varying the concentration of ZnO nanoparticles. In all cases, the antibacterial activity against Gram-positives was greater than against Gram-negatives. Ultrasound-assisted ZnO nanoparticles showed the highest activity, around 99% and 80% for S. aureus and P. aeruginosa, respectively. Similar results were obtained in the study of the anti-inflammatory activity of ZnO nanoparticles; the ultrasound-assisted sample exhibited the highest percentage (93%), even above that shown by diclofenac, which was used as a reference. Therefore, the ZnO nanoparticles synthesized with sargassum extracts have properties that can be used safely and efficiently in the field of biomedicine.

Synthesis of bis(ylidene) cyclohexanones and their antifungal activity against selected plant pathogenic fungi.

Botrytis cinerea, Rhizoctonia solani and Hemileia vastatrix are three species of phytopathogenic fungi behind major crop losses worldwide. These have been selected as target models for testing the fungicide potential of a series of bis(ylidene) cyclohexanones. Although some compounds of this chemical class are known to have inhibitory activity against human pathogens, they have never been explored for the control of phytopathogens until now. In the present work, bis(ylidene) cyclohexanones were synthesized through simple, fast and low-cost base- or acid-catalyzed aldol condensation reaction and tested in vitro against B. cinerea, R. solani and H. vastatrix. bis(pyridylmethylene) cyclohexanones showed the highest activity against the target fungi. When tested at 200 nmol per mycelial plug against R. solani., these compounds completely inhibited the mycelial growth, and the most active bis(pyridylmethylene) cyclohexanone compound had an IC50 of 155.5 nmol plug-1. Additionally, bis(pyridylmethylene) cyclohexanones completely inhibited urediniospore germination of H. vastatrix, at 125 µmol L-1. The most active bis(pyridylmethylene) cyclohexanone had an IC50 value of 4.8 µmol L-1, which was estimated as approximately 2.6 times lower than that found for the copper oxychloride-based fungicide, used as control. Additionally, these substances had a low cytotoxicity against the mammalian Vero cell line. Finally, in silico calculations indicated that these compounds present physicochemical parameters regarded as suitable for agrochemicals. Bis(ylidene) cyclohexanones may constitute promising candidates for the development of novel antifungal agents for the control of relevant fungal diseases in agriculture.

The association of collaterals with myocardial ischemia and viability in chronic total occlusions.

Collateral development in chronic total occlusions (CTO) is crucial to perfuse the distal myocardium and its angiographic evaluation is frequently used to assess the need for revascularization. We aimed to analyse the association between the presence of ischemia and hibernating myocardium, evaluated by cardiac [13 N]NH3/2-[18 F]FDG PET-CT, and the angiographic characterization of the collateral circulation. Prospective study including patients with a CTO who underwent a [13 N]NH3 and, when deemed necessary, 2-[18 F]FDG PET-CT. Well developed (WD) collaterals were defined as a concomitant angiographic Rentrop grade 3 and Werner collateral connection score 2 or 3, whereas the remaining as poorly developed (PD). 2% thresholds used to identify prognostic benefit of revascularization were applied: ischemia > 10% and hibernating myocardium > 7%. Fifty-nine patients (age 62.9±9.1 years, 58 male) were recruited, WD collaterals were present in 28 (47.5%). No significant differences were found in ischemia (WD 6.4±4.3 vs. PD 7.0±4.1, p = 0.64) and hibernation (WD 1.8±1.9 vs. PD 3.1±3.3, p = 0.18) scores. Most CTO territories demonstrated ischemia, but only 19 (46.3%) were associated with an area > 10% (WD 47.6% vs. PD 45.0%, p = 0.58). Scared non-viable myocardium was limited to 9 (15.3%) patients and was not associated with PD collaterals. Hibernating myocardium was frequent (54.2%), but just 6 (10.2%) CTO patients had an area of > 7% (WD 3.6% vs. PD 16.1%, p = 0.20). Collateral assessment by angiography has a poor association with the ischemic burden and hibernation state of CTO territories. Myocardial viability was present even in most CTO with angiographic PD collaterals.