A 3D bioprinted hydrogel gut-on-chip with integrated electrodes for transepithelial electrical resistance (TEER) measurements.

Conventional gut-on-chip (GOC) models typically represent the epithelial layer of the gut tissue, neglecting other important components such as the stromal compartment and the extracellular matrix (ECM) that play crucial roles in maintaining intestinal barrier integrity and function. These models often employ hard, flat porous membranes for cell culture, thus failing to recapitulate the soft environment and complex 3D architecture of the intestinal mucosa. Alternatively, hydrogels have been recently introduced in GOCs as ECM analogs to support the co-culture of intestinal cells inin vivo-like configurations, and thus opening new opportunities in the organ-on-chip field. In this work, we present an innovative GOC device that includes a 3D bioprinted hydrogel channel replicating the intestinal villi architecture containing both the epithelial and stromal compartments of the gut mucosa. The bioprinted hydrogels successfully support both the encapsulation of fibroblasts and their co-culture with intestinal epithelial cells under physiological flow conditions. Moreover, we successfully integrated electrodes into the microfluidic system to monitor the barrier formation in real time via transepithelial electrical resistance measurements.

Adherence to quality indicators for emergency department treatment of acute poisoning according to patient sex. / Grado de cumplimiento de los indicadores de calidad según el sexo del paciente en las intoxicaciones agudas en urgencias.

OBJECTIVES: To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. MATERIAL AND METHODS: Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. RESULTS: A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. CONCLUSION: The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning.

OBJETIVO: Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). METODO: Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. RESULTADOS: Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. CONCLUSIONES: El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo.

Grado de cumplimiento de los indicadores de calidad según el sexo del paciente en las intoxicaciones agudas en urgencias / Adherence to quality indicators for emergency department treatment of acute poisoning according to patient sex

Objetivos. Estudiar las diferencias dependiendo del sexo en la atención de pacientes con intoxicaciones agudas en urgencias y en el grado de cumplimiento de los indicadores de calidad (IC). Método. Estudio observacional y retrospectivo, que incluyó todos los casos de intoxicación aguda de pacientes mayores de 14 años atendidos en el servicio de urgencias de un hospital terciario durante 4 años. Se analizaron variables demográficas, tipo de tóxicos y causa de la intoxicación, el grado de cumplimiento de los IC y destino al alta. Resultados. Se registraron 1.144 casos, un 62,1% (n = 710) eran mujeres. Las mujeres tuvieron mayor número de intoxicaciones voluntarias (52,3% vs 41,4%; p < 0,001) y menos de manera accidental (24,9% vs 30,3%; p = 0,047). Los fármacos más frecuentes en mujeres fueron las benzodiacepinas (49,6% vs 41,2%; p = 0,007), y las intoxicaciones por drogas de abuso y alcohol fueron menores que en hombres. Hubo un alto grado de cumplimiento en la mayoría de los IC (> 85%) en ambos sexos. Conclusiones. El perfil epidemiológico de la intoxicación aguda en mujeres es diferente al de los hombres. En general se puede considerar como óptimo el cumplimiento de los IC en urgencias. No existen diferencias cualitativas en la asistencia del paciente intoxicado con respecto a su sexo. (AU)

Objective. To study differences in the emergency department treatment of acute poisoning according to biological sex of patients and to assess adherence to care quality indicators. Methods. Retrospective observational study including all cases of acute poisoning diagnosed in patients over the age of 14 years treated in a tertiary care hospital emergency department over a period of 4 years. We analyzed demographic variables, substance type and reason for acute poisoning, degree of adherence to quality indicators, and discharge destination. Results. A total of 1144 cases were included; 710 patients (62.1%) were female and 434 (37.9%) were male. The proportion of deliberate self-poisoning was higher in females (52.3% vs 41.4% in males; P < .001); unintentional poisoning was less frequent in females (in 24.9% vs in 30.3% of males; P = .047). Benzodiazepine poisoning was more frequent in females (in 49.6% vs 41.2%; P = .007). Street drug and alcohol poisoning was less common in females. Adherence to quality indicators was high (> 85%) for both sexes. Conclusions. The epidemiologic profile of poisoning is different in females and males. General emergency department adherence to quality indicators can be considered optimal. We detected no qualitative sex-related differences in the care of patients with acute poisoning. (AU)

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Comprehensive splicing analysis of the alternatively spliced CHEK2 exons 8 and 10 reveals three enhancer/silencer-rich regions and 38 spliceogenic variants.

Splicing is controlled by a large set of regulatory elements (SREs) including splicing enhancers and silencers, which are involved in exon recognition. Variants at these motifs may dysregulate splicing and trigger loss-of-function transcripts associated with disease. Our goal here was to study the alternatively spliced exons 8 and 10 of the breast cancer susceptibility gene CHEK2. For this purpose, we used a previously published minigene with exons 6-10 that produced the expected minigene full-length transcript and replicated the naturally occurring events of exon 8 [Δ(E8)] and exon 10 [Δ(E10)] skipping. We then introduced 12 internal microdeletions of exons 8 and 10 by mutagenesis in order to map SRE-rich intervals by splicing assays in MCF-7 cells. We identified three minimal (10-, 11-, 15-nt) regions essential for exon recognition: c.863_877del [ex8, Δ(E8): 75%] and c.1073_1083del and c.1083_1092del [ex10, Δ(E10): 97% and 62%, respectively]. Then 87 variants found within these intervals were introduced into the wild-type minigene and tested functionally. Thirty-eight of them (44%) impaired splicing, four of which (c.883G>A, c.883G>T, c.884A>T, and c.1080G>T) induced negligible amounts (<5%) of the minigene full-length transcript. Another six variants (c.886G>A, c.886G>T, c.1075G>A, c.1075G>T, c.1076A>T, and c.1078G>T) showed significantly strong impacts (20-50% of the minigene full-length transcript). Thirty-three of the 38 spliceogenic variants were annotated as missense, three as nonsense, and two as synonymous, underlying the fact that any exonic change is capable of disrupting splicing. Moreover, c.883G>A, c.883G>T, and c.884A>T were classified as pathogenic/likely pathogenic variants according to ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based criteria. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Dopamine-loaded chitosan-coated solid lipid nanoparticles as a promise nanocarriers to the CNS.

Dopamine is unable to access the central nervous system through the bloodstream. Only its precursor can do so, and with an effectiveness below 100% of the dose administered, as it is metabolized before crossing the blood-brain barrier. In this study, we describe a new solid lipid nanocarrier system designed and developed for dopamine. The nanoparticles were prepared by the melt-emulsification method and then coated with chitosan. The nanocarriers developed had a droplet size of about 250 nm, a polydispersity index of 0.2, a positive surface charge (+30 mV), and a percentage encapsulation efficiency of 36.3 ± 5.4. Transmission and scanning electron microscopy verified uniformity of particle size with spherical morphology. Various types of tests were performed to confirm that the nanoparticles designed are suitable for carrying dopamine through the blood-brain barrier. In vitro tests demonstrated the ability of these nanocarriers to pass through endothelial cell monolayers without affecting their integrity. This study shows that the formulation of dopamine in chitosan-coated solid lipid nanoparticles is a potentially viable formulation strategy to achieve the bioavailability of the drug for the treatment of Parkinson's disease in the central nervous system.

The Impact of the COVID-19 Pandemic on Self-Harm Attempts Observed in a Hospital Emergency Department.

Suicide is a significant public health concern, with one million lives lost to it every year. Suicidal ideation and attempts are markers of high risk. The COVID-19 pandemic has had a negative psychological impact on the population. This study aims to describe and analyze the clinical and sociodemographic characteristics of patients who have received medical attention for self-harm attempts in a hospital emergency department, comparing the period before and after the COVID-19 pandemic. This is a descriptive, retrospective study that collected data from medical records of patients who received care for self-harm attempts in the emergency department. The data included cases from 1 January 2018 to 31 December 2022. In total, 529 cases of self-harm attempts were identified, of which 62.8% were female. The number of post-pandemic self-harm attempts significantly increased compared to the period before the pandemic. The most used method for self-harm was medication ingestion. This study revealed that over one-third of the participants had previously attempted suicide. Most self-harm attempts were made by women in the 10-20 or 41-50 age groups, with a history of psychiatric illness and multiple medications. The study results also highlighted an increase in self-harm attempts during the COVID-19 pandemic.

Chemokine profiling of melanoma-macrophage crosstalk identifies CCL8 and CCL15 as prognostic factors in cutaneous melanoma.

During cancer evolution, tumor cells attract and dynamically interact with monocytes/macrophages. To find biomarkers of disease progression in human melanoma, we used unbiased RNA sequencing and secretome analyses of tumor-macrophage co-cultures. Pathway analysis of genes differentially modulated in human macrophages exposed to melanoma cells revealed a general upregulation of inflammatory hallmark gene sets, particularly chemokines. A selective group of chemokines, including CCL8, CCL15, and CCL20, was actively secreted upon melanoma-macrophage co-culture. Because we previously described the role of CCL20 in melanoma, we focused our study on CCL8 and CCL15 and confirmed that in vitro both chemokines contributed to melanoma survival, proliferation, and 3D invasion through CCR1 signaling. In vivo, both chemokines enhanced primary tumor growth, spontaneous lung metastasis, and circulating tumor cell survival and lung colonization in mouse xenograft models. Finally, we explored the clinical significance of CCL8 and CCL15 expression in human skin melanoma, screening a collection of 67 primary melanoma samples, using multicolor fluorescence and quantitative image analysis of chemokine-chemokine receptor content at the single-cell level. Primary skin melanomas displayed high CCR1 expression, but there was no difference in its level of expression between metastatic and nonmetastatic cases. By contrast, comparative analysis of these two clinically divergent groups showed a highly significant difference in the cancer cell content of CCL8 (p = 0.025) and CCL15 (p < 0.0001). Kaplan-Meier curves showed that a high content of CCL8 or CCL15 in cancer cells correlated with shorter disease-free and overall survival (log-rank test, p < 0.001). Our results highlight the role of CCL8 and CCL15, which are highly induced by melanoma-macrophage interactions in biologically aggressive primary melanomas and could be clinically applicable biomarkers for patient profiling. © 2024 The Pathological Society of Great Britain and Ireland.

Dynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?

INTRODUCTION: The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course. METHODS: The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation. RESULTS: We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7-67.3) for KRAS G12C and 59% (95% CI, 38.5-80.6) for BRAF V600E. CONCLUSIONS: The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Randomized controlled trials in nursing conducted by Latin American research teams: A scoping review.

INTRODUCTION: Randomized controlled trials (RCTs) are the cornerstone of systematic reviews and other evidence synthesis. RCT identification remains challenging because of limitations in their indexation in major databases and potential language bias. Scientific production in Latin American nursing is steadily increasing, but little is known about its design or main features. We aimed to identify the extent of evidence from RCTs in nursing conducted by Latin American research teams and evaluate their main characteristics, including potential risk of bias. DESIGN: Scoping review with risk of bias assessment. METHODS: We conducted a scoping review including a comprehensive electronic search in five relevant databases. We completed a descriptive data analysis and a risk of bias assessment of eligible studies using Cochrane's guidance. RESULTS: We identified 1784 references of which 47 were RCTs published in 40 journals. Twenty (42.6%) RCTs were published in journals in English. Chronic diseases were the most common health conditions studied (29.7%). Fifteen (31.9%) RCTs had a high risk of bias. Thirty (75%) journals were included in the Journal Citation Report (JCR) catalog and 5 (16.7%) were journals classified under nursing category. Twenty-one (52.5%) journals explicitly required CONSORT checklist recommendations for RCTs reporting. CONCLUSION: Publication of RCTs in nursing by Latin American authors has increased. Most journals where RCTs are published are in English and not specific to nursing. Searches in journals of other disciplines may be necessary to facilitate identification of RCTs in nursing. CONSORT statements need to be actively promoted to facilitate rigorous methodology and reporting of RCTs. CLINICAL RELEVANCE STATEMENT: This study highlights the need for an increased research focus on RCTs in nursing in Latin America, and the importance of enhancing the reporting quality of these studies to support evidence-based nursing practice.

Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants.

BACKGROUND: Disrupted pre-mRNA splicing is a frequent deleterious mechanism in hereditary cancer. We aimed to functionally analyze candidate spliceogenic variants of the breast cancer susceptibility gene CHEK2 by splicing reporter minigenes. METHODS: A total of 128 CHEK2 splice-site variants identified in the Breast Cancer After Diagnostic Gene Sequencing (BRIDGES) project (https://cordis.europa.eu/project/id/634935) were analyzed with MaxEntScan and subsetted to 52 variants predicted to impact splicing. Three CHEK2 minigenes, which span all 15 exons, were constructed and validated. The 52 selected variants were then genetically engineered into the minigenes and assayed in MCF-7 (human breast adenocarcinoma) cells. RESULTS: Of 52 variants, 46 (88.5%) impaired splicing. Some of them led to complex splicing patterns with up to 11 different transcripts. Thirty-four variants induced splicing anomalies without any trace or negligible amounts of the full-length transcript. A total of 89 different transcripts were annotated, which derived from different events: single- or multi-exon skipping, alternative site-usage, mutually exclusive exon inclusion, intron retention or combinations of the abovementioned events. Fifty-nine transcripts were predicted to introduce premature termination codons, 7 kept the original open-reading frame, 5 removed the translation start codon, 6 affected the 5'UTR (Untranslated Region), and 2 included missense variations. Analysis of variant c.684-2A > G revealed the activation of a non-canonical TG-acceptor site and exon 6 sequences critical for its recognition. CONCLUSIONS: Incorporation of minigene read-outs into an ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based classification scheme allowed us to classify 32 CHEK2 variants (27 pathogenic/likely pathogenic and 5 likely benign). However, 20 variants (38%) remained of uncertain significance, reflecting in part the complex splicing patterns of this gene.

Light Sheet-Based Laser Patterning Bioprinting Produces Long-Term Viable Full-Thickness Skin Constructs.

Tissue engineering holds great promise for biomedical research and healthcare, offering alternatives to animal models and enabling tissue regeneration and organ transplantation. 3D bioprinting stands out for its design flexibility and reproducibility. Here, an integrated fluorescent light sheet bioprinting and imaging system is presented that combines high printing speed (0.66 mm3 /s) and resolution (9 µm) with light sheet-based imaging. This approach employs direct laser patterning and a static light sheet for confined voxel crosslinking in photocrosslinkable materials. The developed bioprinter enables real-time monitoring of hydrogel crosslinking using fluorescent recovery after photobleaching (FRAP) and brightfield imaging as well as in situ light sheet imaging of cells. Human fibroblasts encapsulated in a thiol-ene click chemistry-based hydrogel exhibited high viability (83% ± 4.34%) and functionality. Furthermore, full-thickness skin constructs displayed characteristics of both epidermal and dermal layers and remained viable for 41 days. The integrated approach demonstrates the capabilities of light sheet bioprinting, offering high speed, resolution, and real-time characterization. Future enhancements involving solid-state laser scanning devices such as acousto-optic deflectors and modulators will further enhance resolution and speed, opening new opportunities in light-based bioprinting and advancing tissue engineering.

The altered sputum microbiome profile in patients with moderate and severe COPD exacerbations, compared to the healthy group in the Indian population.

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson's index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonasand Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

A laboratory framework for ongoing optimization of amplification-based genomic surveillance programs.

IMPORTANCE: This study provides a laboratory framework to ensure ongoing relevance and performance of amplification-based whole genome sequencing to strengthen public health surveillance during extended outbreaks or pandemics. The framework integrates regular reviews of the performance of a genomic surveillance system and highlights the importance of ongoing monitoring and the identification and implementation of improvements to whole genome sequencing methods to enhance public health responses to pathogen outbreaks.

Neuropsychological Assessment of the Relationship of Working Memory with K-BIT Matrices and Vocabulary in Normal Development and ADHD Children and Adolescents.

BACKGROUND: The present report tries to understand the possible relationship between working memory (WM) and intelligence measurements, using the direct scores of the Working Memory Test Battery for Children (WMTBC) and Kaufman's Brief Intelligence Test (K-BIT), in normal development (ND) and diagnosed attention deficit hyperactivity disorder (ADHD) children and adolescents. RESULTS: Partial correlations, discounting the effect of age, showed a significant correlation in ND subjects between the central executive (CE) component of WM and the WM visuospatial sketchpad (VSS) component and the WM phonological loop (PL); also, significant correlations were obtained for the WM VSS with the K-BIT Matrices scores, the WM PL with the K-BIT Vocabulary, and the K-BIT Matrices scores with the K-BIT Vocabulary. For ADHD subjects, there were significant correlations between WM VSS and WM CE, and WM VSS and K-BIT Matrices. We tested the robustness of these correlations by selecting a small number of subjects through permutations; a robust correlation between WM CE and WM PL in ND, and between WM VSS and WM CE and WM VSS and K-BIT Matrices scores was obtained. These results were also supported by mediation analysis. CONCLUSIONS: There is a relationship during development between WM as measured with WMTBC and general intelligence as measured with K-BIT in ND and ADHD subjects. The dysexecutive character of ADHD has been shown, given that by controlling for intelligence, the differences in WM performance between ND and ADHD disappear, except for WM CE. The results suggest that in ADHD subjects, the WM VSS component presents a more pivotal role during cognitive processing compared to ND subjects.

Coffee ground emesis and early endoscopy: Is timing actually relevant? / Vómitos en posos de café y valoración endoscópica precoz. ¿Es realmente el tiempo la clave?

OBJECTIVE: Coffee ground vomiting is a classical symptom of upper gastrointestinal bleeding. However, the clinical usefulness is limited, due to the low positive predictive value. Our goal is to determine if whether an urgent endoscopy does modify our therapeutic management with a real impact on survival. PATIENTS AND METHODS: It is a retrospective, observational and descriptive study. We selected all patients that underwent a gastroscopy in our center for coffee ground vomiting over the last 4 years (2017-2021). Two groups were established: urgent endoscopy (first 24h) and scheduled (over 24h). Then we studied differences between both groups regarding survival, ICU admission, hospitalization days and rebleeding. RESULTS: Three hundred and fourteen patients were identified, from which 276 were included, with 176 belonging to the urgency group and 109 to the scheduled group. There were no differences in the ICU admission, hospitalization days, survival or rebleeding after 30 days. There were no differences either in the number of potentially bleeding lesions or the need of endoscopic therapeutic. CONCLUSIONS: Coffee ground vomiting, without any other data supporting upper gastrointestinal bleeding, does not represent a reliable indicator. Performing urgent endoscopy is not beneficial in terms of morbimortality. Therefore, a more conservative strategy would allow to differ endoscopy, decreasing risks and reducing costs, without affecting the prognosis.

Exploring programmatic indicators of tuberculosis control that incorporate routine Mycobacterium tuberculosis sequencing in low incidence settings: a comprehensive (2017-2021) patient cohort analysis.

Background: Routine whole genome sequencing of Mycobacterium tuberculosis has been implemented with increasing frequency. However, its value for tuberculosis (TB) control programs beyond individual case management and enhanced drug resistance detection has not yet been explored. Methods: We analysed routine sequencing data of culture-confirmed TB cases notified between 1st January 2017 and 31st December 2021 in New South Wales (NSW), Australia. Genomic surveillance included evidence of local TB transmission, defined by single nucleotide polymorphism (SNP) clustering over a variable (0-25) SNP threshold, and drug resistance conferring mutations. Findings: M. tuberculosis sequences from 1831 patients were examined, representing 64.8% of all notified TB cases and 96.2% of culture-confirmed cases. Applying a traditional 5-SNP cluster threshold identified 62 transmission clusters with 183 clustered cases; 101/183 (55.2%) had 0 SNP differences. Cluster assessment over a 5-year period, using a 5-SNP threshold, provided a comprehensive overview of likely recent transmission within NSW, Australia, as an indicator of local TB control. Genotypic drug susceptibility testing (DST) was highly concordant with phenotypic DST and provided a 6.8% increase in antimycobacterial resistance detection. Importantly, it detected mutations missed by routine molecular tests. Lineage 2 strains were more likely to be drug resistant (p < 0.0001) and locally transmitted if drug resistant (p < 0.0001). Interpretation: Performing routine prospective WGS in a low incidence country like Australia, provides genomically informed programmatic indicators of local TB control. A rolling 5-year cluster assessment reflects epidemic containment and progress towards 'zero TB transmission'. Genomic DST also provides valuable information for clinical care and drug resistance surveillance. Funding: NHMRC Centre for Research Excellence in Tuberculosis (www.tbcre.org.au) and NSW Health Prevention Research Support Program.

Internet Addiction and Emotional Intelligence in university nursing students: A cross-sectional study.

Background: The appearance of the Internet has allowed for improved communications and the technological development of society, but it has also led to problematic use, generating addictive behaviors in some university students. Emotional Intelligence helps to improve emotional skills, increase social skills, and act as a protective factor against technological addictions. Objectives: to describe and analyze the relationship between Internet Addiction, Emotional Intelligence, and sociodemographic characteristics in Nursing students. Methods: A multicenter cross-sectional study was conducted. Participants belonged to three different campuses of two Universities. 532 nursing students were included in the study. A self-administered questionnaire was used collecting sociodemographic variables and the TMMS-24 and IAT instruments were employed to measure Emotional Intelligence and Internet Addiction, respectively. Results: 11.1% of the students presented Internet Addiction. Higher Internet Addiction scores were obtained by those who were younger, had a lower academic year, and were more involved in leisure activities. Adequate levels of Emotional Intelligence were found, women showed higher values of Attention and men of Repair. Students aged 24 or over reported higher Clarity and Repair values. There was an inverse relationship between Clarity and Repair with Internet Addiction values. Conclusions: The ability to understand and regulate emotional states is related to lower Internet Addiction values. The group of Internet addicts revealed greater Attention and less Clarity. Internet Addiction values increased as the number of hours of Internet use increases. The development of programs which improve Emotional Intelligence could be essential to facilitate the emotional management of Internet Addiction.

Statistical Analysis and Tokenization of Epitopes to Construct Artificial Neoepitope Libraries.

Epitopes are specific regions on an antigen's surface that the immune system recognizes. Epitopes are usually protein regions on foreign immune-stimulating entities such as viruses and bacteria, and in some cases, endogenous proteins may act as antigens. Identifying epitopes is crucial for accelerating the development of vaccines and immunotherapies. However, mapping epitopes in pathogen proteomes is challenging using conventional methods. Screening artificial neoepitope libraries against antibodies can overcome this issue. Here, we applied conventional sequence analysis and methods inspired in natural language processing to reveal specific sequence patterns in the linear epitopes deposited in the Immune Epitope Database (www.iedb.org) that can serve as building blocks for the design of universal epitope libraries. Our results reveal that amino acid frequency in annotated linear epitopes differs from that in the human proteome. Aromatic residues are overrepresented, while the presence of cysteines is practically null in epitopes. Byte pair encoding tokenization shows high frequencies of tryptophan in tokens of 5, 6, and 7 amino acids, corroborating the findings of the conventional sequence analysis. These results can be applied to reduce the diversity of linear epitope libraries by orders of magnitude.

Commando procedure with posterior atrioventricular groove reconstruction.

This case presents a Commando procedure with posterior atrioventricular groove reconstruction in a patient after double-valve replacement performed in another hospital with a posterior atrioventricular groove patch due to mitral annular calcification for aortomitral Streptococcus agalactiae endocarditis. The patient was transferred to our institution on postoperative day 6 under femoro-axillary venoarterial extracorporeal membrane oxygenation with cardiogenic shock and pulmonary oedema due to patch dehiscence and severe periprosthetic mitral leak. To control pulmonary oedema and decrease myocardial tension, left atrial venting was performed in the intensive care unit through a redo sternotomy. After 24 hours, repeat reconstruction surgery was performed after improvement of pulmonary infiltrates and contractility. We alternate operative images with a porcine wet-lab model to facilitate understanding of this advanced reconstruction.