Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 µM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.

Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.

Classic galactosemia (CG) arises from loss-of-function mutations in the Galt gene, which codes for the enzyme galactose-1-phosphate uridylyltransferase (GALT), a central component in galactose metabolism. The neonatal fatality associated with CG can be prevented by galactose dietary restriction, but for decades it has been known that limiting galactose intake is not a cure and patients often have lasting complications. Even on a low-galactose diet, GALT's substrate galactose-1-phosphate (Gal1P) is elevated and one hypothesis is that elevated Gal1P is a driver of pathology. Here we show that Gal1P levels were elevated above wildtype (WT) in Galt mutant mice, while mice doubly mutant for Galt and the gene encoding galactokinase 1 (Galk1) had normal Gal1P levels. This indicates that GALK1 is necessary for the elevated Gal1P in CG. Another hypothesis to explain the pathology is that an inability to metabolize galactose leads to diminished or disrupted galactosylation of proteins or lipids. Our studies reveal that levels of a subset of cerebrosides-galactosylceramide 24:1, sulfatide 24:1, and glucosylceramide 24:1-were modestly decreased compared to WT. In contrast, gangliosides were unaltered. The observed reduction in these 24:1 cerebrosides may be relevant to the clinical pathology of CG, since the cerebroside galactosylceramide is an important structural component of myelin, the 24:1 species is the most abundant in myelin, and irregularities in white matter, of which myelin is a constituent, have been observed in patients with CG. Therefore, impaired cerebroside production may be a contributing factor to the brain damage that is a common clinical feature of the human disease.

Incidence of incontinence-associated dermatitis in hospitalised neonates. Adaptation and validation of a severity scale.

INTRODUCTION: Up to 60% of hospitalised neonates may develop incontinence-associated dermatitis (IAD). Our aim was to adapt the Clinical Evaluation Scale for Characterization of the Severity of Diaper Dermatitis to the Spanish population and to find out the nationwide frequency of IAD in hospitalized neonates. METHODS: Cross-cultural adaptation and assessment of content validity of the scale. We carried out a prospective, multicentre observational study of the incidence of nappy rash in postnatal wards and neonatal intensive care units in 6 Spanish hospitals. RESULTS: We obtained a content validity index of 0.869 for the total scale (95% CI, 0.742-0.939). The sample included 196 neonates. The cumulative incidence of IAD was 32.1% (9.1% mild-moderate, 8% moderate and 1.6% severe). The incidence rate was 2.2 IAD cases per 100 patient days. A stool pH of less than 5.5, a greater number of bowel movements a day, a greater daily urine output and the use of oral drugs were among the factors associated with the development of IAD. CONCLUSION: The Spanish version of the Clinical Evaluation Scale for Characterization of the Severity of Diaper Dermatitis had an adequate content validity for the assessment of DAI in the hospitalised neonatal population. Mixed feeding, treatment with oral drugs and the use of medical devices in the perianal area were associated with an increased risk of nappy dermatitis in infants.

Percutaneous Endoscopic Gastrostomy with T-Fasteners versus "Pull Technique": Analysis of Complications.

INTRODUCTION: The T-fasteners gastrostomy (T-PEG) has become increasingly popular over recent years as an alternative to the "pull-technique" gastrostomy (P-PEG). This study aimed to compare P-PEG and T-PEG complications. MATERIALS AND METHODS: A retrospective observational study of pediatric patients who underwent percutaneous endoscopic gastrostomy (PEG) placement. P-PEG was performed using the standard Ponsky technique and was replaced after 6 months by a balloon gastrostomy under sedation. T-PEG was performed using three percutaneous T-fasteners (that allow a primary insertion of a balloon gastrostomy). The balloon was replaced by a new one after 6 months without sedation. Complications were recorded. RESULTS: In total, 146 patients underwent PEG placement, 70 P-PEG and 76 T-PEG. The mean follow-up was 3.9 years (standard deviation = 9.6). Age, weight, and associated comorbidities were comparable (p > 0.05). The overall complications were 17 (24.2%) in the P-PEG group and 16 (21.0%) in the T-PEG group (p > 0.05). P-PEG was associated with more sedation for button replacement (97 vs. 2.6% [p < 0.05]). P-PEG was associated with more early tube dislodgement during the first replacement (7.2 vs. 1.4% [p = 0.092]). Two of the five dislodged gastrostomies in the P-PEG group underwent laparotomy due to peritonitis, whereas the only dislodged gastrostomy in the T-PEG group was solved endoscopically. Altogether, P-PEG was associated with more complications that required urgent endoscopy, laparotomy, or laparoscopy (18.6 vs. 6.6% [p < 0.05]). CONCLUSIONS: P-PEG was associated with more sedation, complications during first button replacement, and complications requiring urgent endoscopy, laparotomy, or laparoscopy compared with T-PEG.

Stability of Cesium-Based Lead Halide Perovskites under UV Radiation.

Lead halide perovskites have been extensively studied for their potential applications, including photodetectors, solar cells, and high-energy radiation detection. These applications are possible because of their unique optoelectronic properties, such as tunable band gap, high optical absorption coefficient, and unique defect self-healing properties, which result in high defect tolerance. Despite these advantages, the long-term stability remains a critical issue that could hinder commercial applications of these materials. Reports on the stability of lead halide perovskites for optoelectronic applications have normally focused on methylammonium (MA)/formamidinium (FA), with very limited information for other systems, in particular, Cs-containing perovskites. In this paper, we report the stability of thick CsPbBr3-x Cl x polycrystalline thin films (∼8 µm) with several halide Br-Cl ratios after exposure to deep UV radiation. The chemical, crystal structure, optical, and electrical properties are analyzed, and the results are used to propose a degradation mechanism. The chemical analysis on the surface and bulk of the films indicates the formation of cesium oxide after UV exposure, with no significant change in the crystalline structure. The proposed mechanism explains the formation of cesium oxides during UV exposure. The I-V characteristics of diode structures also showed significant degradation after UV exposure, primarily at lower diode rectification ratios. The mechanism proposed in this paper can contribute to developing strategies to enhance the long-term stability of inorganic lead halide perovskites under UV exposure.

The structure of carbon dioxide at the air-water interface and its chemical implications.

The efficient reduction of CO2 into valuable products is a challenging task in an international context marked by the climate change crisis and the need to move away from fossil fuels. Recently, the use of water microdroplets has emerged as an interesting reaction media where many redox processes which do not occur in conventional solutions take place spontaneously. Indeed, several experimental studies in microdroplets have already been devoted to study the reduction of CO2 with promising results. The increased reactivity in microdroplets is thought to be linked to unique electrostatic solvation effects at the air-water interface. In the present work, we report a theoretical investigation on this issue for CO2 using first-principles molecular dynamics simulations. We show that CO2 is stabilized at the interface, where it can accumulate, and that compared to bulk water solution, its electron capture ability is larger. Our results suggests that reduction of CO2 might be easier in interface-rich systems such as water microdroplets, which is in line with early experimental data and indicate directions for future laboratory studies. The effect of other relevant factors which could play a role in CO2 reduction potential is discussed.

Exploring the mediating role of promoting school physical activity on the relationship between low socioeconomic status and academic achievement and school climate: evidence from 4,990 Chilean schools.

There is evidence that promoting school physical activity (PSPA) benefits children and adolescents, but little is understood about how this promotion may relate to academic achievement and school climate across varying levels of socioeconomic status (SES). Hence, the study aimed to address this knowledge gap by examining two main objectives: (1) determining the association between PSPA and academic achievement and school climate according to schools' SES and (2) exploring the potential mediating role of PSPA in the relationship between schools' SES and academic achievement and school climate. This cross-sectional study at the school level focused on 4,990 schools (including public, subsidized, and private schools) that participated in the National Educational Study 2018 (Chile), which was applied to primary schoolchildren (4th grade, aged 8-10 years). Schools were divided into non-PSPA (n = 4,280) and PSPA (n = 710) during the year 2018. Changes in academic achievement from 2017 to 2018 and school climate were considered. PSPA was associated with improvements in maths (low-SES OR: 1.80, p < 0.001) and reading (middle-SES OR: 1.45, p = 0.029; low-SES OR: 1.47, p < 0.001). The indirect effect (IE) showed that PSPA partially mediated the relationship between SES and academic achievement in reading (IE = 1.017; SE = 0.12; 95%CI, -1.27, -0.77), maths (IE = -1.019; SE = 0.12; 95%CI, -1.25, -0.78), and school climate (IE = -0.46; SE = 0.52; 95%CI, -0.56, -0.35). In conclusion, PSPA was linked to positive changes in academic achievement, especially among low SES, and PSPA presented a potential mediating role in the relationship between SES of schools and academic achievement and school climate.

Advances in the understanding of the production, modification and applications of xylanases in the food industry.

Xylanases have broad applications in the food industry to decompose the complex carbohydrate xylan. This is applicable to enhance juice clarity, improve dough softness, or reduce beer turbidity. It can also be used to produce prebiotics and increase the nutritional value in foodstuff. However, the low yield and poor stability of most natural xylanases hinders their further applications. Therefore, it is imperative to explore higher-quality xylanases to address the potential challenges that appear in the food industry and to comprehensively improve the production, modification, and utilization of xylanases. Xylanases, due to their various sources, exhibit diverse characteristics that affect production and activity. Most fungi are suitable for solid-state fermentation to produce xylanases, but in liquid fermentation, microbial metabolism is more vigorous, resulting in higher yield. Fungi produce higher xylanase activity, but bacterial xylanases perform better than fungal ones under certain extreme conditions (high temperature, extreme pH). Gene and protein engineering technology helps to improve the production efficiency of xylanases and enhances their thermal stability and catalytic properties.

Broadband photodetectors from silane-passivated CsPbBr3 nanocrystals by ultrasound-mediated synthesis.

Perovskite nanocrystals have excellent optical properties but suffer from environmental instability and production up-scaling which limit their commercial application. Here, we report the gram-scale ultrasound-mediated synthesis of silane passivated CsPbBr3 nanocrystals using (3-aminopropyl) triethoxysilane (APTS) as the primary surface ligand surface. The surface engineering endowed the CsPbBr3@SiOR NCs with extended environmental stability, a narrow emission bandwidth and a high photoluminescence quantum yield (PLQY > 75%). Thanks to these excellent optical properties, high-efficiency lateral and vertical photodetectors were fabricated. In particular, the layered vertical photodiode composed of ITO/Ga2O3/CsPbBr3/Au exhibited a broadband photoresponse from 350-700 nm with a responsivity peaking at 44.5.1 A W-1 and specific detectivity above 1013 Jones when illuminated at 470 nm wavelength and biased at +5 V. These results correspond to the best-in-class performance perovskite nanocrystal PD and confirm the extraordinary potential of CsPbBr3@SiOR for the development of efficient optoelectronic devices.

The three-dimensional structure of DapE from Enterococcus faecium reveals new insights into DapE/ArgE subfamily ligand specificity.

DapE is a Zn2+-metallohydrolase recognized as a drug target for bacterial control. It is a homodimer that requires the exchange of interface strands by an induced fit essential for catalysis. Identifying novel anti-DapE agents requires greater structural details. Most of the characterized DapEs are from the Gram-negative group. Here, two high-resolution DapE crystal structures from Enterococcus faecium are presented for the first time with novel aspects. A loosened enzyme intermediate between the open and closed conformations is observed. Substrates may bind to loose state, subsequently it closes, where hydrolysis occurs, and finally, the change to the open state leads to the release of the products. Mutation of His352 suggests a role, along with His194, in the oxyanion stabilization in the mono-metalated Zn2+ isoform, while in the di-metalated isoform, the metal center 2 complements it function. An aromatic-π box potentially involved in the interaction of DapE with other proteins, and a peptide flip could determine the specificity in the Gram-positive ArgE/DapE group. Finally, details of two extra-catalytic cavities whose geometry changes depending on the conformational state of the enzyme are presented. These cavities could be a target for developing non-competitive agents that trap the enzyme in an inactive state.

Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

Biocompatible metal-organic frameworks as promising platforms to eradicate HIV reservoirs ex vivo in people living with HIV.

The HIV attacks the immune system provoking an infection that is considered a global health challenge. Despite antiretroviral treatments being effective in reducing the plasma viral load in the blood to undetectable levels in people living with HIV (PLWH), the disease is not cured and has become chronic. This happens because of the existence of anatomical and cellular viral reservoirs, mainly located in the lymph nodes and gastrointestinal tract, which are composed of infected CD4+ T cells with a resting memory phenotype and inaccessible to antiretroviral therapy. Herein, a new therapeutic strategy based on nanotechnology is presented. Different combinations of antiretroviral drugs (bictegravir/tenofovir/emtricitabine and nevirapine/tenofovir/emtricitabine) and toll-like receptor agonists were encapsulated into metal-organic frameworks (MOFs) PCN-224 and ZIF-8. The encapsulation efficiencies of all the drugs, as well as their release rate from the carriers, were measured. In vitro studies about the cell viability, the hemocompatibility, and the platelet aggregation of the MOFs were carried out. Epifluorescence microscopy assays confirmed the ability of ZIF-8 to target a carboxyfluorescein probe inside HeLa cell lines and PBMCs. These results pave the way for the use of these structures to eliminate latent HIV reservoirs from anatomical compartments through the activation of innate immune cells, and a higher efficacy of the triplet combinations of antiretroviral drugs.

Triplet State Radical Chemistry: Significance of the Reaction of 3SO2 with HCOOH and HNO3.

The triplet excited states of sulfur dioxide can be accessed in the UV region and have a lifetime large enough that they can react with atmospheric trace gases. In this work, we report high level ab initio calculations for the reaction of the a3B1 and b3A2 excited states of SO2 with weak and strong acidic species such as HCOOH and HNO3, aimed to extend the chemistry reported in previous studies with nonacidic H atoms (water and alkanes). The reactions investigated in this work are very versatile and follow different kinds of mechanisms, namely, proton-coupled electron transfer (pcet) and conventional hydrogen atom transfer (hat) mechanisms. The study provides new insights into a general and very important class of excited-state-promoted reactions, opening up interesting chemical perspectives for technological applications of photoinduced H-transfer reactions. It also reveals that atmospheric triplet chemistry is more significant than previously thought.

Delineation of intracavitary electrograms for the automatic quantification of decrement-evoked potentials in the coronary sinus with deep-learning techniques.

Cardiac arrhythmias cause depolarization waves to conduct unevenly on the myocardial surface, potentially delaying local components with respect to a previous beat when stimulated at faster frequencies. Despite the diagnostic value of localizing the distinct local electrocardiogram (EGM) components for identifying regions with decrement-evoked potentials (DEEPs), current software solutions do not perform automatic signal quantification. Electrophysiologists must manually measure distances on the EGM signals to assess the existence of DEEPs during pacing or extra-stimuli protocols. In this work, we present a deep learning (DL)-based algorithm to identify decrement in atrial components (measured in the coronary sinus) with respect to their ventricular counterparts from EGM signals, for disambiguating between accessory pathways (APs) and atrioventricular re-entrant tachycardias (AVRTs). Several U-Net and W-Net neural networks with different configurations were trained on a private dataset of signals from the coronary sinus (312 EGM recordings from 77 patients who underwent AP or AVRT ablation). A second, separate dataset was annotated for clinical validation, with clinical labels associated to EGM fragments in which decremental conduction was elucidated. To alleviate data scarcity, a synthetic data augmentation method was developed for generating EGM recordings. Moreover, two novel loss functions were developed to minimize false negatives and delineation errors. Finally, the addition of self-attention mechanisms and their effect on model performance was explored. The best performing model was a W-Net model with 6 levels, optimized solely with the Dice loss. The model obtained precisions of 91.28%, 77.78% and of 100.0%, and recalls of 94.86%, 95.25% and 100.0% for localizing local field, far field activations, and extra-stimuli, respectively. The clinical validation model demonstrated good overall agreement with respect to the evaluation of decremental properties. When compared to the criteria of electrophysiologists, the automatic exclusion step reached a sensitivity of 87.06% and a specificity of 97.03%. Out of the non-excluded signals, a sensitivity of 96.77% and a specificity of 95.24% was obtained for classifying them into decremental and non-decremental potentials. Current results show great promise while being, to the best of our knowledge, the first tool in the literature allowing the delineation of all local components present in an EGM recording. This is of capital importance at advancing processing for cardiac electrophysiological procedures and reducing intervention times, as many diagnosis procedures are performed by comparing segments or late potentials in subsequent cardiac cycles.

miR-218-5p, miR-124-3p and miR-23b-3p act synergistically to modulate the expression of NACC1, proliferation, and apoptosis in C-33A and CaSki cells.

Background: In cervical cancer (CC), miR-218-5p, -124-3p, and -23b-3p act as tumor suppressors. These miRNAs have specific and common target genes that modulate apoptosis, proliferation, invasion, and migration; biological processes involved in cancer. Methods: miR-218-5p, -124-3p, and -23b-3p mimics were transfected into C-33A and CaSki cells, and RT-qPCR was used to quantify the level of each miRNA and NACC1. Proliferation was assessed by BrdU and apoptosis by Annexin V/PI. In the TCGA and The Human Protein Atlas databases, the level of NACC1 mRNA and protein (putative target of the three miRNAs) was analyzed in CC and normal tissue. The relationship of NACC1 with the overall survival in CC was analyzed in GEPIA2. NACC1 mRNA and protein levels were higher in CC tissues compared with cervical tissue without injury. Results: An increased expression of NACC1 was associated with lower overall survival in CC patients. The levels of miR-218-5p, -124-3p, and -23b-3p were lower, and NACC1 was higher in C-33A and CaSki cells compared to HaCaT cells. The increase of miR-218-5p, -124-3p, and -23b-3p induced a significant decrease in NACC1 mRNA. The transfection of the three miRNAs together caused more drastic changes in the level of NACC1, in the proliferation, and in the apoptosis with respect to the individual transfections of each miRNA. Conclusion: The results indicate that miR-218-5p, -124-3p, and -23b-3p act synergistically to decrease NACC1 expression and proliferation while promoting apoptosis in C-33A and CaSki cells. The levels of NACC1, miR-218-5p, -124-3p, and -23b-3p may be a potential prognostic indicator in CC.

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

[Strategies for the prevention and non-pharmacological treatment of diabetes. Models of care]. / Estrategias para la prevención y tratamiento no farmacológico de la diabetes. Modelos de atención.

Diabetes is a highly prevalent, chronic disease that over time generates potentially serious complications. In the treatment of diabetes, the use of drugs that have shown significant benefits is important, but, in addition, the use of non-pharmacological interventions is essential, which constitute an efficient and effective way to reduce the appearance of diabetes itself and the complications of the disease. These interventions, which are described here, include health education, aimed at incorporating a healthier lifestyle, dietary modifications, increased physical activity or psychological support. Finally, the characteristics that a care system for people with diabetes must meet to achieve the established objectives are discussed.