Endothelial Biomarkers in Critically Ill COVID-19 Patients: Potential Predictors of the Need for Dialysis.

INTRODUCTION: The aim of this was to evaluate the function of vascular biomarkers to predict the need for hemodialysis in critically ill patients with COVID-19. METHODS: This is a prospective study with 58 critically ill patients due to COVID-19 infection. Laboratory tests in general and vascular biomarkers, such as VCAM-1, syndecan-1, angiopoietin-1, and angiopoietin-2, were quantified on intensive care unit (ICU) admission. RESULTS: There was a 40% death rate. VCAM and Ang-2/Ang-1 ratio on ICU admission were associated with the need for hemodialysis. Vascular biomarkers (VCAM-1, syndecan-1, angiopoietin-2/angiopoietin-1 ratio) were predictors of death and their cutoff values were useful to stratify patients with a worse prognosis. In the multivariate cox regression analysis with adjusted models, VCAM-1 (OR 1.13 [CI 95%: 1.01-1.27]; p = 0.034) and Ang-2/Ang-1 ratio (OR 4.87 [CI 95%: 1.732-13.719]; p = 0.003) were associated with the need for dialysis. CONCLUSION: Vascular biomarkers, mostly VCAM-1 and Ang-2/Ang-1 ratio, showed better efficiency to predict the need for hemodialysis in critically ill COVID-19 patients.

Incidence of congenital and postnatal cytomegalovirus infection during the first year of life in Mexican preterm infants.

Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high-income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18-sequences clustered in five distinct clades (A-E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.

Mechanistic perspectives on differential mitochondrial-based neuroprotective effects of several carnitine forms in Alzheimer's disease in vitro model.

Mitochondrial deregulation has emerged as one of the earliest pathological events in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Improvement of mitochondrial function in AD has been considered a relevant therapeutic approach. L-carnitine (LC), an amino acid derivative involved in the transport of long-chain fatty acids into mitochondria, was previously demonstrated to improve mitochondrial function, having beneficial effects in neurological disorders; moreover, acetyl-L-carnitine (ALC) is currently under phase 4 clinical trial for AD (ClinicalTrials.gov NCT01320527). Thus, in the present study, we investigated the impact of different forms of carnitines, namely LC, ALC and propionyl-L-carnitine (PLC) on mitochondrial toxicity induced by amyloid-beta peptide 1-42 oligomers (AßO; 1 µM) in mature rat hippocampal neurons. Our results indicate that 5 mM LC, ALC and PLC totally rescued the mitochondrial membrane potential and alleviated both the decrease in oxygen consumption rates and the increase in mitochondrial fragmentation induced by AßO. These could contribute to the prevention of neuronal death by apoptosis. Moreover, only ALC ameliorated AßO-evoked changes in mitochondrial movement by reducing the number of stationary mitochondria and promoting reversal mitochondrial movement. Data suggest that carnitines (LC, ALC and PLC) may act differentially to counteract changes in mitochondrial function and movement in neurons subjected to AßO, thus counteracting AD-related pathological phenotypes.

Respiratory Syncytial Virus-A ON1 Genotype Emergence in Central Mexico in 2009 and Evidence of Multiple Duplication Events.

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections. An RSV-A genotype (ON1) that contains a 72-nt duplication was reported in 2012 and has since extended worldwide. Methods: We analyzed 345 respiratory samples obtained between 2003 and 2014 to assess the relevance of ON1 infections. Nucleotidic and deduced amino acid sequences from viruses detected in San Luis Potosí and sequences previously reported were analyzed. Results: RSV ON1 was detected in 105 samples. The earliest case of ON1 infection was detected in November 2009, almost 1 year prior to detection of this virus in Canada. Amino acid sequence analysis of the duplication region showed the presence of Y273N and L274P substitutions in RSV GA2 viruses that, when combined, resulted in 4 different GXXSPSQ sequence motifs at positions 272-278. Three of these motifs were present in both the original and duplicated regions of ON1 strains. Additional signature amino acid substitutions were observed in ON1 strains that have the different sequence motifs. Conclusions: ON1 strains include viruses that appear to be the result of at least 3 independent duplication events. Molecular data of strains from diverse geographical regions should help define the frequency and implications of this evolution mechanism.

Effect of cytomegalovirus infection and leukocyte immunoglobulin like receptor B1 polymorphisms on receptor expression in peripheral blood mononuclear cells.

Leukocyte immunoglobulin like receptor B1 (LILRB1) plays a significant role in a number of infectious, autoimmune, cardiovascular, and oncologic disorders. LILRB1 expression varies between individuals and may be associated with polymorphisms on the regulatory region of the LILRB1 gene, as well as to previous cytomegalovirus infection. In this study, the contribution of these two factors to LILRB1 expression in peripheral blood mononuclear cells of healthy young adults was analyzed. LILRB1 expression in NK cells, T cells, B cells and monocytes was significantly stronger in individuals who had had cytomegalovirus infection than in those who had not (P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Overall, no differences in LILRB1 expression were observed between individuals with and without GAA haplotypes of the LILRB1 regulatory region. However, when analyzed according to cytomegalovirus infection status, significant differences in LILRB1+ NK cells were observed. A higher proportion of LILRB1+ cells was found in GAA+ than in GAA- individuals who had not been infected (P < 0.01), whereas GAA- individuals had a larger proportion of LILRB1+ cells than GAA+ individuals who were cytomegalovirus positive (P < 0.01). In conclusion, cytomegalovirus infection has a major effect on LILRB1 expression in NK and other mononuclear cells and polymorphisms in the LILRB1 regulatory region appear to have a modulatory influence over this effect.

The carboxylic acid transporters Jen1 and Jen2 affect the architecture and fluconazole susceptibility of Candida albicans biofilm in the presence of lactate.

Candida albicans has the ability to adapt to different host niches, often glucose-limited but rich in alternative carbon sources. In these glucose-poor microenvironments, this pathogen expresses JEN1 and JEN2 genes, encoding carboxylate transporters, which are important in the early stages of infection. This work investigated how host microenvironments, in particular acidic containing lactic acid, affect C. albicans biofilm formation and antifungal drug resistance. Multiple components of the extracellular matrix were also analysed, including their impact on antifungal drug resistance, and the involvement of both Jen1 and Jen2 in this process. The results show that growth on lactate affects biofilm formation, morphology and susceptibility to fluconazole and that both Jen1 and Jen2 might play a role in these processes. These results support the view that the adaptation of Candida cells to the carbon source present in the host niches affects their pathogenicity.

Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease.

Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.

NK cell immunophenotypic and genotypic analysis of infants with severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants. Reduced numbers of NK cells have been reported in infants with severe RSV infection; however, the precise role of NK cells during acute RSV infection is unclear. In this study the NK and T cell phenotypes, LILRB1 gene polymorphisms and KIR genotypes of infants hospitalized with RSV infection were analyzed. Compared to controls, infants with acute RSV infection showed a higher proportion of LILRB1+ T cells; in addition, a subgroup of infants with RSV infection showed an increase in LILRB1+ NK cells. No differences in NKG2C, NKG2A, or CD161 expression between RSV infected infants and controls were observed. LILRB1 genotype distribution of the rs3760860 A>G, and rs3760861 A>G single nucleotide polymorphisms differed between infants with RSV infection and healthy donors, whereas no differences in any of the KIR genes were observed. Our results suggest that LILRB1 participates in the pathogenesis of RSV infection. Further studies are needed to define the role of LILRB1+ NK in response to RSV and to confirm an association between LILRB1 polymorphisms and the risk of severe RSV infection.

Outbreak of Clostridium difficile PCR ribotype 027--the recent experience of a regional hospital.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, and several outbreaks with increased severity and mortality have been reported. In this study we report a C. difficile PCR ribotype 027 outbreak in Portugal, aiming to contribute to a better knowledge of the epidemiology of this agent in Europe. METHODS: Outbreak report with retrospective study of medical records and active surveillance data of all inpatients with the diagnosis of CDI, from 1st January to 31th December 2012, in a Portuguese hospital. C. difficile isolates were characterized regarding ribotype, toxin genes and moxifloxin resistance. Outbreak control measures were taken, concerning communication, education, reinforcement of infection control measures, optimization of diagnosis and treatment of CDI, and antibiotic stewardship. RESULTS: Fifty-three inpatients met the case definition of C. difficile-associated infection: 55% males, median age was 78.0 years (interquartile range: 71.0-86.0), 75% had co-morbidities, only 15% had a nonfatal condition, 68% had at least one criteria of severe disease at diagnosis, 89% received prior antibiotherapy, 79% of episodes were nosocomial. CDI rate peak was 13.89/10,000 bed days. Crude mortality rate at 6 months was 64.2% while CDI attributable cause was 11.3%. Worse outcome was related to older age (P = 0.022), severity criteria at diagnosis (leukocytosis (P = 0.008) and renal failure), and presence of fatal underlying condition (P = 0.025). PCR ribotype 027 was identified in 16 of 22 studied samples. CONCLUSIONS: This is the first report of a 027-CDI outbreak in Portugal. We emphasize the relevance of the measures taken to control the outbreak and highlight the importance of implementing a close and active surveillance of CDI.

The transport of carboxylic acids and important role of the Jen1p transporter during the development of yeast colonies.

On solid substrates, yeast colonies pass through distinct developmental phases characterized by the changes in pH of their surroundings from acidic to nearly alkaline and vice versa. At the beginning of the alkali phase colonies start to produce ammonia, which functions as a quorum-sensing molecule inducing the reprogramming of cell metabolism. Such reprogramming includes, among others, the activation of several plasma membrane transporters and is connected with colony differentiation. In the present study, we show that colony cells can use two transport mechanisms to import lactic acid: a 'saturable' component of the transport, which requires the presence of a functional Jen1p transporter, and a 'non-saturable' component (diffusion) that is independent of Jen1p. During colony development, the efficiency of both transport components changes similarly in central and outer colonial cells. Although the lactate uptake capacity of central cells gradually decreases during colony development, the lactate uptake capacity of outer cells peaks during the alkali phase and is also kept relatively high in the second acidic phase. This lactate uptake profile correlates with the localization of the Jen1p transporter to the plasma membrane of colony cells. Both lactic acid uptake mechanisms are diminished in sok2 colonies where JEN1 expression is decreased. The Sok2p transcription factor may therefore be involved in the regulation of non-saturable lactic acid uptake in yeast colonies.

A meta-analysis on the role of sonication in the diagnosis of cardiac implantable electronic device-related infections.

Introduction: One of the biggest obstacles in diagnosing Implant-Associated Infections is the lack of infection criteria and standardized diagnostic methods. These infections present a wide range of symptoms, and their diagnosis can be hampered by the formation of microbial biofilms on the surface of implants. This study aimed to provide insight into the performance of sonication in the diagnosis of infections associated with Cardiac Implantable Electronic Devices, to help define a consensus on the algorithm for the microbial diagnosis of these infections. Methods: We carried out a systematic review with meta-analysis. The PRISMA methodology guidelines were followed, and an advanced search was carried out in PubMed and Web of Science, which enabled 8 articles to be included in the review, in which a meta-analysis was also carried out. QUADAS-2 was used to assess the risk of bias and effect measures were calculated to assess publication bias. Results: The overall sensitivity of the method was 0.823 (95% CI: 0.682-0.910) and the specificity was 0.632 (95% CI: 0.506-0.743). Discussion: These results suggest that sonication may offer advantages in diagnosing these infections. However, it is essential to approach these findings carefully and take into account the recommendations provided in the EHRA 2019 guidelines. This study highlights the importance of more effective diagnostic approaches for implantable medical device-associated infections to improve the quality of treatment and minimize the risks associated with these challenging medical conditions.

Endothelium-related biomarkers enhanced prediction of kidney support therapy in critically ill patients with non-oliguric acute kidney injury.

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients.

Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

BACKGROUND: The clinical picture of coronavirus disease 2019 (COVID-19)-associated sepsis is similar to that of sepsis of other aetiologies. The present study aims to analyse the role of syndecan-1 (SDC-1) as a potential predictor of septic shock in critically ill patients with COVID-19. METHODS: This is a prospective study of 86 critically ill patients due to COVID-19 infection. Patients were followed until day 28 of hospitalization. Vascular biomarkers, such as vascular cell adhesion protein-1, SDC-1, angiopoietin-1 and angiopoietin-2, were quantified upon admission and associated with the need for vasopressors in the first 7 d of hospitalization. RESULTS: A total of 86 patients with COVID-19 (mean age 60±16 y; 51 men [59%]) were evaluated. Thirty-six (42%) patients died during hospitalization and 50 (58%) survived. The group receiving vasopressors had higher levels of D-dimer (2.46 ng/ml [interquartile range {IQR} 0.6-6.1] vs 1.01 ng/ml [IQR 0.62-2.6], p=0.019) and lactate dehydrogenase (929±382 U/l vs 766±312 U/l, p=0.048). The frequency of deaths during hospitalization was higher in the group that received vasoactive amines in the first 24 h in the intensive care unit (70% vs 30%, p=0.002). SDC-1 levels were independently associated with the need for vasoactive amines, and admission values >269 ng/ml (95% CI 0.524 to 0.758, p=0.024) were able to predict the need for vasopressors during the 7 d following admission. CONCLUSIONS: Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

Uncovering the Early Events Associated with Oligomeric Aß-Induced Src Activation.

Soluble Aß1-42 oligomers (AßO) are formed in the early stages of Alzheimer's disease (AD) and were previously shown to trigger enhanced Ca2+ levels and mitochondrial dysfunction via the activation of N-methyl-D-aspartate receptors (NMDAR). Src kinase is a ubiquitous redox-sensitive non-receptor tyrosine kinase involved in the regulation of several cellular processes, which was demonstrated to have a reciprocal interaction towards NMDAR activation. However, little is known about the early-stage mechanisms associated with AßO-induced neurodysfunction involving Src. Thus, in this work, we analysed the influence of brief exposure to oligomeric Aß1-42 on Src activation and related mechanisms involving mitochondria and redox changes in mature primary rat hippocampal neurons. Data show that brief exposure to AßO induce H2O2-dependent Src activation involving different cellular events, including NMDAR activation and mediated intracellular Ca2+ rise, enhanced cytosolic and subsequent mitochondrial H2O2 levels, accompanied by mild mitochondrial fragmentation. Interestingly, these effects were prevented by Src inhibition, suggesting a feedforward modulation. The current study supports a relevant role for Src kinase activation in promoting the loss of postsynaptic glutamatergic synapse homeostasis involving cytosolic and mitochondrial ROS generation after brief exposure to AßO. Therefore, restoring Src activity can constitute a protective strategy for mitochondria and related hippocampal glutamatergic synapses.

Antioxidants in Sunscreens: Which and What For?

Ultraviolet (UV) radiation promotes the generation of reactive oxygen species (ROS) and nitrogen species (RNS), resulting in skin damage. Cosmetic industries have adopted a strategy to incorporate antioxidants in sunscreen formulations to prevent or minimize UV-induced oxidative damage, boost photoprotection effectiveness, and mitigate skin photoaging. Many antioxidants are naturally derived, mainly from terrestrial plants; however, marine organisms have been increasingly explored as a source of new potent antioxidant molecules. This work aims to characterize the frequency of the use of antioxidants in commercial sunscreens. Photoprotective formulations currently marketed in parapharmacies and pharmacies were analyzed with respect to the composition described on the label. As a result, pure compounds with antioxidant activity were found. The majority of sunscreen formulations contained antioxidants, with vitamin E and its derivatives the most frequent. A more thorough analysis of these antioxidants is also provided, unveiling the top antioxidant ingredients found in sunscreens. A critical appraisal of the scientific evidence regarding their effectiveness is also performed. In conclusion, this work provides an up-to-date overview of the use of antioxidants in commercial sunscreens for a better understanding of the advantages associated with their use in photoprotective formulations.

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives.

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs' formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.

Urine-derived stem cells in neurological diseases: current state-of-the-art and future directions.

Stem cells have potential applications in the field of neurological diseases, as they allow for the development of new biological models. These models can improve our understanding of the underlying pathologies and facilitate the screening of new therapeutics in the context of precision medicine. Stem cells have also been applied in clinical tests to repair tissues and improve functional recovery. Nevertheless, although promising, commonly used stem cells display some limitations that curb the scope of their applications, such as the difficulty of obtention. In that regard, urine-derived cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, their obtaining can be challenging due to the low yield and complexity of the multi-phased and typically expensive differentiation protocols. As an alternative, urine-derived stem cells (UDSCs), included within the population of urine-derived cells, present a mesenchymal-like phenotype and have shown promising properties for similar purposes. Importantly, UDSCs have been differentiated into neuronal-like cells, auspicious for disease modeling, while overcoming some of the shortcomings presented by other stem cells for these purposes. Thus, this review assesses the current state and future perspectives regarding the potential of UDSCs in the ambit of neurological diseases, both for disease modeling and therapeutic applications.

Restoration of c-Src/Fyn Proteins Rescues Mitochondrial Dysfunction in Huntington's Disease.

Aims: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder with no effective therapies. Mutant huntingtin protein (mHTT), the main HD proteinaceous hallmark, has been linked to reactive oxygen species (ROS) formation and mitochondrial dysfunction, among other pathological mechanisms. Importantly, Src-related kinases, c-Src and Fyn, are activated by ROS and regulate mitochondrial activity. However, c-Src/Fyn involvement in HD is largely unexplored. Thus, in this study, we aimed at exploring changes in Src/Fyn proteins in HD models and their role in defining altered mitochondrial function and dynamics and redox regulation. Results: We show, for the first time, that c-Src/Fyn phosphorylation/activation and proteins levels are decreased in several human and mouse HD models mainly due to autophagy degradation, concomitantly with mHtt-expressing cells showing enhanced TFEB-mediated autophagy induction and autophagy flux. c-Src/Fyn co-localization with mitochondria is also reduced. Importantly, the expression of constitutive active c-Src/Fyn to restore active Src kinase family (SKF) levels improves mitochondrial morphology and function, namely through improved mitochondrial transmembrane potential, mitochondrial basal respiration, and ATP production, but it did not affect mitophagy. In addition, constitutive active c-Src/Fyn expression diminishes the levels of reactive species in cells expressing mHTT. Innovation: This work supports a relevant role for c-Src/Fyn proteins in controlling mitochondrial function and redox regulation in HD, revealing a potential HD therapeutic target. Conclusion: c-Src/Fyn restoration in HD improves mitochondrial morphology and function, precluding the rise in oxidant species and cell death. Antioxid. Redox Signal. 38, 95-114.

Comparative Studies on the Photoreactivity, Efficacy, and Safety of Depigmenting Agents.

Depigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents-4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid-for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay. In vitro tyrosinase inhibition was compared, and cell viability was assessed in B-16V melanocytes to evaluate safety. Results showed 4-butylresorcinol, ascorbyl glucoside, and α-arbutin are non-photoreactive, while for ascorbic acid and bakuchiol it was not possible to reach conclusive results due to the lack of specificity of the ROS assay. 4-Butylresorcinol, acting as a competitive inhibitor, displayed potent tyrosinase inhibition, followed by ascorbic acid and bakuchiol. Both 4-butylresorcinol and bakuchiol reduced cell viability in a concentration-dependent manner. The insights obtained in this work support the development of depigmenting products by providing useful scientific guidance on the photostability, tyrosinase inhibitory efficacy, and skin safety of depigmenting agents.

Syndecan-1 predicts hemodynamic instability in critically ill patients under intermittent hemodialysis.

Introduction: Up to 70% of intermittent hemodialysis (IHD) sessions in critically ill patients are complicated by hemodynamic instability. Although several clinical characteristics have been associated with hemodynamic instability during IHD, the discriminatory capacity of predicting such events during IHD sessions is less defined. In the present study, we aimed to analyse endothelium-related biomarkers collected before IHD sessions and their capacity to predict hemodynamic instability related to IHD in critically ill patients. Methods: In this prospective observational study, we enrolled adult critically ill patients with acute kidney injury who required fluid removal with IHD. We screened each included patient daily for IHD sessions. Thirty minutes before each IHD session, each patient had a 5-mL blood collection for measurement of endothelial biomarkers-vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-1 and -2 (AGPT1 and AGPT2) and syndecan-1. Hemodynamic instability during IHD was the main outcome. Analyses were adjusted for variables already known to be associated with hemodynamic instability during IHD. Results: Plasma syndecan-1 was the only endothelium-related biomarker independently associated with hemodynamic instability. The accuracy of syndecan-1 for predicting hemodynamic instability during IHD was moderate [area under the receiver operating characteristic curve 0.78 (95% confidence interval 0.68-0.89)]. The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.67 to 0.82 (P < .001) and improved risk prediction, as measured by net reclassification improvement. Conclusion: Syndecan-1 is associated with hemodynamic instability during IHD in critically ill patients. It may be useful to identify patients who are at increased risk for such events and suggests that endothelial glycocalyx derangement is involved in the pathophysiology of IHD-related hemodynamic instability.