The expression of immune response genes in patients with chronic Chagas disease is shifted toward the levels observed in healthy subjects as a result of treatment with Benznidazole.

Introduction: Chagas disease, caused by the Trypanosoma cruzi parasite infection, is a potentially life-threatening neglected tropical disease with a worldwide distribution. During the chronic phase of the disease, there exists a fragile balance between the host immune response and parasite replication that keeps patients in a clinically-silent asymptomatic stage for years or even decades. However, in 40% of patients, the disease progresses to clinical manifestations mainly affecting and compromising the cardiac system. Treatment is recommended in the chronic phase, although there are no early markers of its effectiveness. The aim of this study is to identify differential expression changes in genes involved in the immune response in antigen-restimulated PBMC from chronic patients with Chagas disease due to benznidazole treatment. Methods: Thus, high-throughput real-time qPCR analysis has been performed to simultaneously determine global changes in the expression of 106 genes involved in the immune response in asymptomatic (IND) and early cardiac manifestations (CCC I) Chagas disease patients pre- and post-treatment with benznidazole. Results and discussion: The results revealed that 7 out of the 106 analyzed genes were differentially expressed (4 up- and 3 downregulated) after treatment in IND patients and 15 out of 106 (3 up- and 12 downregulated) after treatment of early cardiac Chagas disease patients. Particularly in CCC I patients, regulation of the expression level of some of these genes towards a level similar to that of healthy subjects suggests a beneficial effect of treatment and supports recommendation of benznidazole administration to early cardiac Chagas disease patients. The data obtained also demonstrated that both in asymptomatic patients and in early cardiac chronic patients, after treatment with benznidazole there is a negative regulation of the proinflammatory and cytotoxic responses triggered as a consequence of T. cruzi infection and the persistence of the parasite. This downregulation of the immune response likely prevents marked tissue damage and healing in early cardiac patients, suggesting its positive effect in controlling the pathology.

Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study).

Although, in randomized clinical trials, once-weekly subcutaneous semaglutide (OW s.c.) has demonstrated superior efficacy in comparison with placebo and active controls in terms of glycemic control and body weight reduction in patients with type 2 diabetes mellitus (T2DM), these results need to be confirmed in a real-world (RW) setting. An RW ambispective study (6 months retrospective and 6 months prospective) was conducted in 10 tertiary hospitals in Spain. We evaluated changes in HbA1c and body weight in patients with T2DM treated with semaglutide OW s.c. Additionally, we analyzed different subgroups of patients treated with semaglutide OW s.c. as an add-on to glucose-lowering therapy. A total of 752 patients with a mean age of 60.2 years, a mean HbA1c level of 8.5%, a mean body weight of 101.6 kg, and a mean T2DM duration of 10 years were included. At 12 months, compared with baseline, there was a mean difference of -2.1% in HbA1c levels (p < 0.001) and a mean difference of 9.2 kg in body weight (p < 0.001). Moreover, there were statistically significant differences (p < 0.001) between baseline and month 12 in both HbA1c and body weight in the four subgroups receiving semaglutide OW s.c. as an add-on to glucose-lowering therapy. Semaglutide OW s.c. was well tolerated, with gastrointestinal disorders being the most commonly reported side effects. In this RW study, 12 months of treatment with semaglutide OW s.c. in patients with T2DM was associated with significant and clinically relevant improvements in glycemic control and weight loss, regardless of the glucose-lowering therapy received, and the overall safety profile was positive.

The Mediating Role of Cardiorespiratory Fitness in the Association between a Negative Lifestyle and Poor Mental Health in Chilean Schoolchildren.

BACKGROUND: A negative lifestyle has a reported relationship with psychological problems and deteriorated well-being. However, there is little information regarding the mediating role of cardiorespiratory fitness (CRF) in this relationship. OBJECTIVES: The objectives of the present study are twofold: first, to investigate the association between negative lifestyle, physical self-concept (PSC), and depression, and second, to assess the potential mediating role of CRF in this complex relationship. METHODS: This cross-sectional study included 612 schoolchildren aged between 9 and 14 years from the Araucanía region (southern Chile). CRF was measured using the Leger test, and lifestyle, depression, and PSC were measured using validated questionnaires. RESULTS: A negative lifestyle reported an inverse association with PSC (p < 0.001) and a positive association with depression levels (p < 0.001). The mediation analysis showed that CRF was positively related to PSC (p < 0.001) and inversely related to depression (p = 0.001); besides, the indirect effect CRF acted as a partial mediator in the association between a negative lifestyle and PSC (indirect effect = -1.15; SE = 0.01; 95% CI, -1.87, -0.55) and depression levels (indirect effect = 0.22; SE = 0.08; 95% CI, 0.08, 0.38). CONCLUSION: In conclusion, CRF in schoolchildren played a potential mediating role in the association between a negative lifestyle and depression and PSC.

External Validation of the Machine Learning-Based Thermographic Indices for Rheumatoid Arthritis: A Prospective Longitudinal Study.

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices-Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)-based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients.

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.

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.

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.

Barriers and Strategies to Optimize the Use of Glucagon-Like Peptide 1 Receptor Agonists in People with Type 2 Diabetes and High Cardiovascular Risk or Established Cardiovascular Disease: A Delphi Consensus in Spain.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for glycemic control, with many also demonstrating cardiovascular (CV) benefit, in people with type 2 diabetes (T2D). This study aimed to find a consensus on the barriers and strategies for the optimal use of GLP-1 RAs in people with T2D and high CV risk or established cardiovascular disease (CVD) in Spain. METHODS: A two-round Delphi survey (53 questions) was conducted among members of four national scientific societies in Spain, including physicians experienced in the management of people with T2D. The degree of consensus was evaluated with a 7-point Likert scale, establishing consensus when ≥ 70% of the panelists agreed (6-7) or disagreed (1-2). RESULTS: A total of 97 physicians participated in the first round (endocrinology: 34%, family and community medicine: 21%, internal medicine: 23%, and cardiology: 23%), and 96 in the second round. The main barriers identified were: therapeutic inertia and late use of GLP-1 RAs; lack of a comprehensive approach to CV risk; lack of knowledge on the usefulness of GLP-1 RAs in CVD prevention and treatment; and economic/administrative barriers. Strategies with a highest consensus included: the need to establish simple protocols that integrate awareness of CV risk monitoring; training professionals and patients; and the use of new technologies. CONCLUSION: Physicians identified clinical, healthcare, and economic/administrative barriers that limit the use of GLP-1 RAs in people with T2D and high CV risk or established CVD in Spain, highlighting the importance of integrating these therapies according to clinical practice guidelines.

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 suggest 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.

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.

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.

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.

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.

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.

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.

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.