The RNA from Pseudomonas aeruginosa reduces neutrophil responses favoring bacterial survival.

INTRODUCTION: Epithelial and endothelial cells modulate innate immune responses in the lung, including the arrival of neutrophils (PMN), which are crucial cells for the antibacterial host defense. Cells are exposed to prokaryotic RNA (pRNA) during bacterial infections and different pRNA may promote or attenuate the inflammatory response on different immune cells. Pseudomonas aeruginosa (PAE) can cause severe pneumonia and has several immune-evading mechanisms. The aim of this study was to determine the effects of the RNA from PAE (RNAPAE) on lung epithelial, endothelial cells, and PMN, and its impact on bacterial elimination. METHODS: Purified total RNAPAE was used as a stimulus on a human lung epithelial cell line (Calu-6), human microvascular endothelial cell line HMEC-1 and isolated healthy human PMN. Activation and cytokine secretion were evaluated. In addition, PMN elimination of live ECO or PAE was determined in the presence of RNAPAE. RESULTS: We found that RNAPAE either induced a pro-inflammatory response on Calu-6 and HMEC-1 or PMN. Pre-stimulation of PMN with RNAPAE diminished activation and chemotaxis induced by live bacteria. Moreover, we found that RNAPAE reduced phagocytosis of live ECO. Finally, we also found that non-degraded fragments of small RNA (<200 bp) were responsible for the PMN microbicidal attenuation during PAE elimination. CONCLUSION: Our results indicated that short fragments of RNAPAE diminished the immune response of PMN favoring bacterial survival.

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Real-world implementation of North American and SIOP strategies for the treatment of Wilms tumor in Uruguay.

Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.

Evolution of ambiguity tolerance research a scientometric and bibliometric analysis.

Introduction: The present study conducts a retrospective bibliometric analysis to examine the quantifiable and qualitative evolution of the concept of tolerance to ambiguity (TA) over time. Additionally, a scientometric analysis using quantitative methods on scientific measurements and trends aims to profile and identify the concept, as well as its development in research themes. The relevance of this study is underscored by the growing interest and development of research on TA, particularly in fields like entrepreneurship where psychological factors are significant. Methods: The research includes highly relevant literature, such as Budner and Frenkel-Brunswick, which define TA as a predisposition to perceive ambiguous situations as desirable and as a personality variable centered on the emotional and perceptual domain, respectively. Data was obtained from the eight indices comprising the main Web of Science collection, covering research from 1975 to December 2022. A total of 378 articles were identified. Results: The analysis reveals that scientific production peaked in 2022 with 45 articles. In terms of citations, 7,773 were found, with the highest concentration in 2022, totaling 1,203 citations. This indicates a significant increase in research interest and output related to TA. Discussion: The study highlights the growing exploration of the concept of TA, emphasizing its importance across multiple disciplines in dealing with uncertainty. The research demonstrates that TA significantly influences decision-making and adaptability, highlighting its value in business and educational settings. By analyzing leading publications, authors, and research centers, the study shows the diversity of approaches to understanding TA, indicating a promising direction for future research.

Radiotherapy in the treatment of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy. OBJECTIVE: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy. METHODS: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy. RESULTS: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids. CONCLUSION: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy.

Use of Extracellular Monomeric Ubiquitin as a Therapeutic Option for Major Depressive Disorder.

Major depressive disorder (MDD) is a mood disorder that has become a global health emergency according to the World Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and financial loss. Patients with MDD present immunoendocrine alterations like cortisol resistance and inflammation, which are associated with alterations in neurotransmitter metabolism. There are currently numerous therapeutic options for patients with MDD; however, some studies suggest a high rate of therapeutic failure. There are multiple hypotheses explaining the pathophysiological mechanisms of MDD, in which several systems are involved, including the neuroendocrine and immune systems. In recent years, inflammation has become an important target for the development of new therapeutic options. Extracellular monomeric ubiquitin (emUb) is a molecule that has been shown to have immunomodulatory properties through several mechanisms including cholinergic modulation and the generation of regulatory T cells. In this perspective article, we highlight the influence of the inflammatory response in MDD. In addition, we review and discuss the evidence for the use of emUb contained in Transferon as a concomitant treatment with selective serotonin reuptake inhibitors (SSRIs).

Ocular manifestations of juvenile Sjögren's disease.

PURPOSE OF REVIEW: This review aims to enhance understanding of juvenile Sjögren's disease (jSjD) by exploring diagnostic criteria, ocular clinical features, ancillary ophthalmic testing, and management strategies specific to this rare pediatric condition. RECENT FINDINGS: Unlike adults, children with jSjD often present with recurrent parotitis and extra-glandular symptoms before developing sicca symptoms. Adult SjD classification criteria do not consider pediatric-specific symptoms and physiological differences. Underutilization of diagnostic tests such as the ocular staining score (OSS) and Schirmer I may result in an incomplete understanding of the prevalence of keratoconjunctivitis sicca in jSjD. SUMMARY: Timely referral to an ophthalmologist can address perceived feasibility issues with respect to ocular features in jSjD. Management of keratoconjunctivitis sicca in jSjD includes improving ocular surface lubrication and decreasing inflammation. Recognition of pediatric-specific clinical features and development of universally accepted jSjD classification criteria will allow for better identification of potential participants for future jSjD studies.

Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model.

Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). P. berghei ANKA (PbA) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8+ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of Entamoeba hystolitica. Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8+ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8+ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.

Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

To Preserve or Extract? A Scoping Review and a Prognostic Decision Tool using Multispecialty Indicators.

As implant-supported restorations have become very popular, there is a tendency to extract teeth and replace them with implants. However, the first goal of dentistry should always be the preservation of natural teeth, given the prerequisite that these can be maintained with the application of appropriate treatment modalities. Therefore, individual tooth risk assessment and prognosis are very important in the treatment plan process. Four important factors influencing the dentist's decision on whether to save or extract a compromised tooth have been identified, and an extensive search of the related English language literature has been performed. Additionally, hand-search in related journals was implemented, and classical textbooks were consulted. Identified articles on patient-related, periodontal, endodontic, and restorative factors were thoroughly analyzed, focusing on diagnosis and tooth prognosis. Fifty-two selected references have been carefully selected and reviewed. Available information was used to develop a color-coded prognostic decision chart with four different factors and up to fourteen crucial parameters. All factors and parameters were analyzed in an effort to help the restorative dentist make a prognostic decision. The proposed color-coded prognostic decision chart can be helpful when a treatment plan is made, and predictable restorative care is planned. This comprehensive prognostic decision chart can aid dentists in providing clinical care of high quality and establishing a consensus on available restorative options. It can additionally establish appropriate communication with patients and third-party individuals in the restorative care process, effectively manage risk factors, and provide a framework for quality assessment in restorative treatment.

The lack of EphB3 receptor prevents bone loss in mouse models of osteoporosis.

Bone homeostasis is a complex process in which some Eph kinase receptors and their ephrin ligands appear to be involved. In the present study, we address this issue by examining, both in vitro and in vivo, the role of EphB2 and EphB3 in mesenchymal stromal/stem cell (MSC) differentiation into bone tissue. This was first evaluated by quantitative reverse transcription PCR (RT-qPCR) and histological staining in MSCs cultured in specific mediums revealing that although EphB2-/- MSCs mainly expressed pro-adipogenic transcription factors, EphB3-/- MSCs showed abundant osteogenic transcripts, such as Runx2, Msx2, and Sp7. To clarify the underlying molecular mechanisms, we found that the lack of EphB3 signaling alters the genetic profile of differentiating MSCs, reducing the expression of many inhibitory molecules and antagonists of the BMP signaling pathway, and increasing Bmp7 expression, a robust bone inductor. Then, to confirm the osteogenic role of EphB3 in vivo, we studied the condition of 2 mouse models of induced bone loss (ovariectomy or long-term glucocorticoid treatment). Interestingly, in both models, both WT and EphB2-/- mice equally developed the disease but EphB3-/- mice did not exhibit the typical bone loss, nor an increase in urine Ca2+ or blood serum CTX-1. This phenotype in EphB3-KO mice could be due to their significantly higher proportions of osteoprogenitor cells and preosteoblasts, and their lower number of osteoclasts, as compared with WT and EphB2-KO mice. Thus, we conclude that EphB3 acts as a negative regulator of the osteogenic differentiation, and its absence prevents bone loss in mice subjected to ovariectomy or dexamethasone treatment.

Osteoporosis affects more than 200 million people, mostly women. Our work shows that the EphB3 receptor restricts bone formation, and its absence prevents bone loss in osteoporotic mice. The bone protection observed in EphB3-deficient mice is due to the presence of more bone-forming cells and fewer bone-degrading cells. Molecularly, we found that when there's no EphB3 in mesenchymal stem cells, some bone-promoting genes are increased while many inhibitors are reduced. Therefore, this receptor could become a key target for new therapies that would help to improve the quality of life for those suffering from bone diseases. We're really excited to share our findings with a broad audience, including patients, healthcare professionals, researchers, and the life sciences industry.

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).

Monomeric ubiquitin (Ub) is a 76-amino-acid highly conserved protein found in eukaryotes. The biological activity of Ub first described in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations, compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes, have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, and cardio- and brain-protective agent.

Sociodemographic Disparities in Tracheostomy Timing and Outcomes.

OBJECTIVE: Tracheostomies are commonly performed in critically ill patients requiring prolonged mechanical ventilation. Although early tracheostomy has been associated with improved outcomes, the reasons for delayed tracheostomy are complex. We examined the impact of sociodemographic factors on tracheostomy timing and outcomes. METHODS: Medical records were retrospectively reviewed of ventilator-dependent adult patients who underwent tracheostomy from 2021 to 2022. Tracheostomy timing was defined as routine (<21 days) versus late (21 days or more). Sociodemographic variables were compared between cohorts using univariate and multivariate models. Secondary outcomes included hospital length of stay (LOS), decannulation, tracheostomy-related complications, and inhospital mortality. RESULTS: One hundred forty-two patients underwent tracheostomy after initial intubation: 74.7% routine (n = 106) and 25.4% late (n = 36). In a multivariate model adjusted for age, race, surgical service, tracheostomy technique, and time between consultation and surgery, non-English speaking patients and women were more likely to receive a late tracheostomy compared with English speaking patients and men, respectively (odds ratio [OR] 3.18, 95% confidence interval [CI] 1.03, 9.81, p < 0.05), (OR 3.15, 95% CI 1.18, 8.41, p < 0.05). Late tracheostomy was associated with longer median hospital LOS (62 vs. 52 days, p < 0.05). Tracheostomy timing did not significantly impact mortality, decannulation or tracheostomy-related complications. CONCLUSION: Despite an association between earlier tracheostomy and shorter LOS, non-English speaking patients and female patients are more likely to receive a late tracheostomy. Standardized protocols for tracheostomy timing may address bias in the referral and execution of tracheostomy and reduce unnecessary hospital days. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:582-587, 2024.

Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs.

In Uruguay, the pediatric acute lymphoblastic leukemia (ALL) cure rate is 82.2%, similar to those reported in developed countries. However, many patients suffer adverse effects that could be attributed, in part, to genetic variability. This study aims to identify genetic variants related to drugs administered during the induction phase and analyze their contribution to adverse effects, considering individual genetic ancestry. Ten polymorphisms in five genes (ABCB1, CYP3A5, CEP72, ASNS, and GRIA1) related to prednisone, vincristine, and L-asparaginase were genotyped in 200 patients. Ancestry was determined using 45 ancestry informative markers (AIMs). The sample ancestry was 69.2% European, 20.1% Native American, and 10.7% African, but with high heterogeneity. Mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry. Mucositis was significantly associated with ASNS (rs3832526; 3R/3R vs. 2R carriers; OR: = 6.88 [1.88-25.14], p = 0.004) and CYP3A5 (non-expressors vs. expressors; OR: 4.55 [1.01-20.15], p = 0.049) genes. Regarding Cushing syndrome, patients with the TA genotype (rs1049674, ASNS) had a higher risk of developing Cushing syndrome than those with the TT genotype (OR: 2.60 [1.23-5.51], p = 0.012). Neurotoxicity was significantly associated with ABCB1 (rs9282564; TC vs. TT; OR: 4.25 [1.47-12.29], p = 0.007). Moreover, patients with <20% Native American ancestry had a lower risk of developing neurotoxicity than those with ≥20% (OR: 0.312 [0.120-0.812], p = 0.017). This study shows the importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia.

Inspiratory muscle training in patients with obesity: a systematic review and meta-analysis.

Introduction: Obesity is a chronic medical condition that affects, among others, the cardiovascular and respiratory systems. Interventions for its treatment focus on sustained weight reduction and general health improvement, leaving respiratory management aside. Our objective was to determine the effects of inspiratory muscle training (IMT) in patients with obesity. Methods: A systematic review was performed in Embase, Cochrane Library (CENTRAL), CINAHL, Web of Science, and PubMed/MEDLINE on June 26, 2023. Randomized clinical trials (RCTs), and quasi-randomized clinical trials investigating the effects of IMT in people with obesity were included. Selected studies were screened by two independent reviewers who extracted data and assessed the quality of the evidence. Results: The initial search returned 705 potential studies were included. Ultimately, eight studies met the criteria for eligibility and were included in the review. IMT improves physical capacity [6-minute walk test (6MWT): 44.5 m, 95% CI: 30.5 to 58.5; p < 0.0001] and the strength of the inspiratory muscles [maximal inspiratory pressure (MIP): -28.4 cm H2O, 95% CI: -41.9 to -14.8; p < 0.0001] compared to the controls, without differences in the pulmonary function, body mass index (BMI) and metabolic parameters. Conclusion: Inspiratory muscle training improves physical capacity and inspiratory muscle strength without significant changes in lung function, BMI, and metabolic parameters.Systematic review registration: PROSPERO, identifier CRD42023439625, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439625.

Intracranial progression of the epidermoid cyst to a white epidermoid cyst in a pediatric patient: a case report.

BACKGROUND: Epidermoid cysts are rare benign lesions that originate from remnants of ectodermal epithelial tissue, particularly infrequent in the pediatric population. They exhibit characteristic imaging features, with occasional variations leading to the development of a "white" epidermoid cyst. This transformation results from the presence of protein and lipid material within the cyst, causing intrinsic hyperintensity in T1-weighted images, signal hypointensity in T2-weighted images, and a bright signal in diffusion-weighted imaging. CASE PRESENTATION: We describe the case of a 5-year-old Latina pediatric patient initially diagnosed with a typical epidermoid cyst. After 13 years of follow-up, this typical epidermoid cyst underwent a transformation, becoming a "white" epidermoid cyst. CONCLUSIONS: Epidermoid cysts are rare intracranial lesions. The term "white epidermoid cyst" does not denote a variant; it represents a distinct transformation within an epidermoid cyst due to liquid and protein accumulation. This transformation should be considered in cases with specific imaging characteristics.

Effect of COGNI-MACHINE computational thinking training on executive functions in children aged 9 to 11: Protocol of a cluster randomized controlled trial.

We designed a controlled trial protocol that seeks to contribute to cognitive science by studying the effect of thought training on children's executive functions. The study design is a cluster randomized controlled trial, with intra-subject and inter-subject evaluation, with two parallel groups: an experimental group and a TAU control group. With three measures, pre-test, post-test, and follow-up after three months. The participants will be children aged 9 to 11. The allocation will be randomized by groups and not individually. The sample will be a minimum of 44 participants. The primary measures will be neuropsychological tests to assess executive functions. Secondary measures will be a computational thinking test, neuropsychological tests to assess metacognition and attention, and an acceptability scale. The experimental group will participate in the COGNI-MACHINE computational thinking training designed by the first author. The training frequency will be twice a week in 60 min sessions for 12 weeks. The TAU control group will receive computer science classes as usual during the same time as the experimental group. The evaluators taking the measurements will be blinded to the assignment. The investigators in charge of the intervention will be blinded to the results of the evaluations.

In vitro activity of ceftazidime-avibactam against Gram-negative strains in Chile 2015-2021.

OBJECTIVES: Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible ß-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. Using data from the Antimicrobial Testing Leadership and Surveillance program (ATLAS), this study examined the in vitro antimicrobial activity of CAZ-AVI and other antibiotics against Gram-negative bacteria collected from Chilean hospitals between 2015 and 2021. METHODS: Clinical isolates of Enterobacterales and P. aeruginosa were collected from three medical centres in Chile. Blood, abdominal fluid, urine, soft tissues, and respiratory tract samples were obtained from infected patients. Minimum inhibitory concentrations using the broth microdilution method were determined for susceptibility testing, and the Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for interpreting the results. Extended-spectrum ß-lactamases (ESBL) and carbapenemase genes were also detected through polymerase chain reaction. RESULTS: A total of 2600 Enterobacterales and 836 P. aeruginosa were analysed. CAZ-AVI was the antibiotic with the highest in vitro activity against Enterobacterales (99.72%). The incidence of carbapenem-resistant Enterobacterales (CRE) was 1.5% (n = 39), and the antibiotics with the best in vitro activity were tigecycline (92.31%), CAZ-AVI (88.57%), and amikacin (79.49%). CAZ-AVI was the antibiotic with the best activity against ESBL-producing Enterobacterales (99.34%) and MDR Enterobacterales (99.31%). For KPC-producing Enterobacterales, susceptibility to amikacin was 100%, whereas susceptibility to CAZ-AVI was 91.67%. Regarding MDR and difficult-to-treat resistance P. aeruginosa, 44.83% and 38.99% were susceptible to CAZ-AVI, respectively. CONCLUSION: CAZ-AVI shows excellent in vitro activity against Enterobacterales in general, CRE, ESBL-producing Enterobacterales, and KPC-producing Enterobacterales. CAZ-AVI is also an option against MDR P. aeruginosa.

Diagnostic Performance of Serum MicroRNAs for ST-Segment Elevation Myocardial Infarction in the Emergency Department.

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.