Nonsense CD247 mutations show dominant-negative features in TCR expression and function.

BACKGROUND: The invariant TCRζ/CD247 homodimer is crucial for TCR/CD3 expression and signaling through its three immunoreceptor tyrosine-based activation motifs (ITAMs). Homozygous null mutations in CD247 lead to immunodeficiency, while carriers exhibit 50% reduced surface CD3. It is unclear whether carriers of other CD247 variants show dominant-negative effects. OBJECTIVE: To analyze and model the potential impact on TCR expression and function of heterozygous nonsense CD247 mutations found in patients with signs of immunodeficiency or autoimmunity. METHODS: Jurkat T cells, either wild-type (WT) or CRISPR/Cas9-edited CD247-deficient (ZKO), were lentivirally transduced with wild-type CD247 or mutations ablating one (Q142X), two (Q101X), or three (Q70X) ITAMs. RESULTS: Three patients from unrelated families were studied. Two heterozygous nonsense CD247 mutations were identified (p.Y152X and p.Q101X), which affected ITAM-3 and ITAM-2+3, respectively. Both mutations were associated with low surface CD3 expression, normal intracellular CD247 levels using a transmembrane-specific antibody but very low intracellular CD247 levels using an ITAM-3-specific one, suggesting the presence of truncated variants in T cells. Transduction of the mutations lacking 1, 2, or 3 ITAMs into ZKO could not restore normal surface CD3 expression (only 60%, 22% and 10%, respectively), whereas in WT they reduced it (to 39%, 19% and 9% of normal levels), and both effects were ITAM number dependent. All six transfectants showed reduced CD69 induction (25-50%), indicating that they were unable to signal downstream properly neither isolated nor associated with wild-type CD247. CONCLUSION: Our results suggest that CD247 variants lacking ITAMs due to nonsense, but not null, mutations are defective for normal TCR assembly and exert a dominant-negative effect on TCR expression and signaling in vitro. This, in turn, may correlate with clinical features in vivo.

Age-related changes in brain oscillatory patterns during an n-back task in children and adolescents.

The development of brain oscillatory responses and their possible role in the working memory (WM) performance of children, adolescents and young adults was investigated. A set of 0- and 1-back tasks with letter stimuli were administered to a final sample of 131 subjects (between 6 and 20 years of age). A decrease in response times (RTs) and an increase of the sensitivity index d-prime (d') were seen with increased age. RTs increased and d' decreased with load, indicating higher difficulty for higher loads. Event-related synchronization (ERS) and event-related desynchronization (ERD) were obtained by the convolution of Morlet wavelets on the recorded EEG. Statistical analyses were performed of the absolute and relative power of brain oscillations defined by topography, frequency and latency. Posterior alpha and beta ERD, and frontocentral theta ERS, were induced by the stimuli presented during the n-back task. While relative theta ERS increased with age, absolute theta ERS, absolute and relative alpha and, absolute beta ERD, decreased with age. Age-related improvement in behavioral performance was mediated by relative theta. Alpha and beta ERD were more pronounced for the most difficult task (1-back) and for the target condition. Globally, there was high consistency of the effects of target type and task load across development. Theta ERS maturation is a crucial step for improving WM performance during development, while alpha and beta ERD maturation seem to be less critical for behavioral performance improvement with age, possibly due to a sufficient level of alpha-beta ERD for good performance in young children.

Prevalence of crystal deposits in asymptomatic hyperuricemia according to different scanning definitions: A comparative study.

BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

Real-world and game-based learning to enhance decision-making.

BACKGROUND: The evolving healthcare landscape necessitates highly qualified nurses equipped with a myriad of soft skills, including decision-making. Traditional teaching models have led to innovative, active methods that prioritise student participation and enhance crucial soft skill development, such as decision- making. Considering the recognised importance of improving clinical decision-making skills and the need for innovative training, a literature gap is present in assessing the effect of real world and game-based learning on decision-making abilities. OBJECTIVES: This study aimed to investigate the effect of real-world and game-based learning, specifically using case-based learning and escape room, on decision-making competence in postgraduate nursing students in academic and clinical settings. DESIGN: A descriptive, cross-sectional, quantitative intervention study was conducted, combining case-based learning and escape room methods sequentially. SETTINGS: The study was conducted among postgraduate nursing students at the University of Navarra in Spain. PARTICIPANTS: Sixty-six postgraduate nursing students, mostly women, participated in the study. METHODS: The study integrated case-based learning and escape room sequentially. Data were collected through an ad hoc online questionnaire, recorded escape times from the escape room, and academic scores. RESULTS: The study enrolled 66 participants with an average professional experience of 4.2 years. Academic results showed high scores in case resolution (average: 8.34) and knowledge tests (average: 9.21). Out of 11 groups, 81.8 % successfully escaped the escape room within 30 min, with positive questionnaire responses indicating enthusiasm, enjoyment and perceived effectiveness of the activities. CONCLUSIONS: Real-world and game-based learning significantly enhanced decision-making competence in postgraduate nursing students across academic and clinical settings, demonstrating the importance of diverse teaching methods. Further research, including comparative studies and longitudinal analyses, is needed to evaluate the educational benefits of integrating case-based learning and escape room methods in nurse education and to refine assessment tools while monitoring long-term student progress.

An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Physical Activity in Patients with Advanced Cancer: Sociodemographic, Clinical, and Psychological Correlates.

As cancer progresses, patients may experience physical decline, which can impair their ability to carry out essential daily tasks. The aim of this study was to analyze the levels of physical activity in patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A prospective, cross-sectional, multicenter study was carried out in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and psychological scales. In total, 508 patients were included in the study, the majority of whom were male, over the age of 65, and diagnosed with bronchopulmonary tumors (36%) and metastatic disease. Based on their physical activity levels, participants were categorized as sedentary (20%, n = 190), engaging in light physical activity (43%, n = 412), or demonstrating moderate physical activity (37%, n = 351). Patients who were over 65 years old; had a worse baseline status (ECOG ≥ 1); lacked a partner; had a lower educational level; or were retired or unemployed were found to have lower levels of physical activity. Those with sedentary physical activity reported higher levels of psychological distress, anxiety, depression, somatization, and physical symptoms, as well as worse functional status, global health status, and well-being. Understanding the complex interplay between physical activity and sociodemographic, clinical, and psychological factors can help neuroscientists develop tailored exercise interventions that address the unique needs of advanced cancer patients.

Promotion of Healthy Habits in University Students: Literature Review.

The increase in responsibilities, together with the multiple challenges that students face in the university period, has a direct impact on their healthy lifestyles. This literature review describes the benefits of promoting healthy habits in college, highlighting the fundamental role of prevention and promotion. A systematic review was carried out following the PRISMA recommendations, searching for information in the WOS and Scopus databases. On the other hand, a search was carried out within the existing and available grey literature. The review focused on finding information about physical activity, nutrition, and stress (with an emphasis on resilience and academic burnout) in university students. This bibliographic review includes 32 articles and six web pages, containing information on the benefits of physical activity, healthy habits, and health prevention. The information collected in this study shows that university students are exposed to multiple changes during this period, increasing as the academic years progress. At that time, their habits worsen, with low adherence to the Mediterranean diet, low physical activity, and high levels of stress, specifically increasing cases of academic burnout. The establishment of healthy habits during the university period is necessary, observing an improvement in all the variables studied. Prevention has played a fundamental role.

Resilience, Burnout and Mental Health in Nurses: A Latent Mediation Model.

Background/Objectives: The burnout syndrome in nurses has been related to the development of mental health problems. On the contrary, resilience is related to adequately coping with stressful situations and better mental health. The objective was to analyze the relationship between resilience and mental health problems in nurses and estimate the proportion mediated by burnout in the association. Methods: In 2021, a total of 1165 Spanish nurses were selected through a stratified random sampling method. Participants anonymously filled in the Resilience Scale (RS-14), the Maslach Burnout Inventory Survey, and the General Health Questionnaire. To test the hypothesis proposed and explain the mediating effect of burnout empirically, structural equation modeling (SEM) was applied. A latent mediation model was computed. Results: Resilience was negatively related to burnout and mental health problems. The direct relationship between burnout and the latent health variable was positive. In addition, in view of the total effect of resilience on mental health problems and the magnitude of the indirect effect, we stated that the proportion of this effect mediated by burnout ranged from 0.486 to 0.870. Conclusions: This study reveals that fostering resilience in nurses directly and indirectly reduces burnout and improves their mental health. The implementation of resilience programs and supportive institutional policies is recommended to improve working conditions and the quality of patient care.

Chloroquine-induced DNA damage synergizes with DNA repair inhibitors causing cancer cell death.

Background: Cancer is a global health problem accounting for nearly one in six deaths worldwide. Conventional treatments together with new therapies have increased survival to this devastating disease. However, the persistent challenges of treatment resistance and the limited therapeutic arsenal available for specific cancer types still make research in new therapeutic strategies an urgent need. Methods: Chloroquine was tested in combination with different drugs (Panobinostat, KU-57788 and NU-7026) in 8 human-derived cancer cells lines (colorectal: HCT116 and HT29; breast: MDA-MB-231 and HCC1937; glioblastoma: A-172 and LN-18; head and neck: CAL-33 and 32816). Drug´s effect on proliferation was tested by MTT assays and cell death was assessed by Anexin V-PI apoptosis assays. The presence of DNA double-strand breaks was analyzed by phospho-H2AX fluorescent staining. To measure homologous recombination efficiency the HR-GFP reporter was used, which allows flow cytometry-based detection of HR stimulated by I-SceI endonuclease-induced DSBs. Results: The combination of chloroquine with any of the drugs employed displayed potent synergistic effects on apoptosis induction, with particularly pronounced efficacy observed in glioblastoma and head and neck cancer cell lines. We found that chloroquine produced DNA double strand breaks that depended on reactive oxygen species formation, whereas Panobinostat inhibited DNA double-strand breaks repair by homologous recombination. Cell death caused by chloroquine/Panobinostat combination were significantly reduced by N-Acetylcysteine, a reactive oxygen species scavenger, underscoring the pivotal role of DSB generation in CQ/LBH-induced lethality. Based on these data, we also explored the combination of CQ with KU-57788 and NU-7026, two inhibitors of the other main DSB repair pathway, nonhomologous end joining (NHEJ), and again synergistic effects on apoptosis induction were observed. Conclusion: Our data provide a rationale for the clinical investigation of CQ in combination with DSB inhibitors for the treatment of different solid tumors.

Increase in invasive Haemophilus influenzae serotype A infections during the COVID-19 pandemic in New South Wales, Australia.

Haemophilus influenzae, a causative agent of severe invasive infections such as meningitis, sepsis and pneumonia, is classified into encapsulated or typeable (represented by serotypes A to F) and non-typeable varieties (NTHi) by the presence or absence of the polysaccharide capsule. Invasive disease caused by H. influenzae type B (HIB) can be prevented through vaccination which remains the main disease control intervention in many countries. This study examined the genomic diversity of circulating H. influenzae strains associated with invasive disease in New South Wales, Australia, before and during the COVID-19 pandemic. Ninety-six isolates representing 95 cases of invasive H. influenzae infections (iHi) diagnosed between January 2017 and September 2022 were typed and characterised using whole genome sequencing. These cases were caused by serotypes A (n=24), B (n=35), E (n=3), F (n=2) and NTHi (n=32). There was an apparent decline in the number of iHi infections during the COVID-19 pandemic, with a corresponding increase in the proportion of iHi cases caused by serotype A (HIA), which returned to pre-pandemic levels in 2022. Fifteen isolates associated with HIB or non-typeable iHi were resistant to ß-lactams due to a PBP3 mutation or carriage of blaTEM-1. Further, capsular gene duplication was observed in HIB isolates but was not found in HIA. These findings provide important baseline genomic data for ongoing iHi surveillance and control.

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

Objetivo Los vómitos en posos de café son un síntoma clásico de hemorragia digestiva alta. Sin embargo, tienen escasa validez semiológica, dado su conocido bajo valor predictivo positivo. Nuestro objetivo es determinar si realizar una gastroscopia urgente en estos pacientes modifica nuestra conducta terapéutica con impacto real en la morbimortalidad. Pacientes y métodos Se trata de un estudio retrospectivo, observacional y descriptivo en el que se analizaron aquellos pacientes que se realizaron una gastroscopia en nuestro centro por vómitos en posos de café en los últimos 4 años (2017-2021). Se establecieron 2 grupos: endoscopia urgente (primeras 24h) y programada (más de 24h) y se evaluaron las diferencias entre ambos grupos en supervivencia, estancia en la UCI, días de ingreso hospitalario y tasa de resangrado. Resultados Se identificaron 314 pacientes, de los que finalmente se incluyeron 276, perteneciendo 176 al grupo de gastroscopia urgente y 109 al de diferida. No se identificaron diferencias en la tasa de ingreso en la UCI, días de estancia hospitalaria, supervivencia ni resangrado a los 30 días. Tampoco se objetivaron diferencias en la tasa de detección de lesiones potencialmente sangrantes ni en la necesidad de terapéutica endoscópica. Conclusiones Los vómitos en posos de café, sin otros datos clínicos de hemorragia digestiva, no son un indicador fiable de la misma, y la realización de una gastroscopia urgente no aporta beneficios en términos de morbimortalidad. Una estrategia conservadora en estos pacientes permitiría diferir endoscopias, evitando riesgos y ayudando al control de gastos sin incidir en el pronóstico del paciente. (AU)

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. (AU)

An Anatomical Study Using Computed Tomography, Magnetic Resonance Imaging, and Rhinoscopy of the Nasal Cavity of Domestic Cat (Felis silvestris catus L.) and Big Cats: Lion (Panthera leo leo L.), Leopard (Panthera pardus kotiya L.), and Cheetah (Acinonyx jubatus jubatus S.).

The objective of this work was to study the normal anatomy of the nasal cavity of the three species of big cats (leopard, lion, and cheetah) compared to the domestic cat through the use of computed tomography, magnetic resonance imaging, and rhinoscopy. Computed tomography allowed us to clearly visualize the entire bony and cartilaginous framework that supports the nasal cavity. Magnetic resonance imaging permitted better visualization of the soft tissues of this cavity. On the other hand, rhinoscopy enabled the direct visualization of the mucosa of the vestibule and nasal cavity, which is very useful in the diagnosis of masses or foreign bodies. Furthermore, with this technique, it has been possible to observe several small orifices from the nasolacrimal duct, the pharyngeal auditory tube, and the lateral nasal gland. Computed tomography, magnetic resonance imaging, and rhinoscopy are useful tools in analysis of the anatomical characteristics of the nasal cavity in these species.

Lack of Specific Immune Response after Five Doses of mRNA SARS-CoV-2 Vaccine in a Patient with CD4+ T-Cell Lymphopenia but Preserved Responses to CMV.

Immunogenicity of SARS-CoV-2 mRNA vaccines is highly heterogeneous in patients with inborn errors of immunity (IEIs). This case report analyzes the immune response to mRNA COVID-19 two-dose primary vaccination followed by three boosters in an IEI patient with marked CD4+ T-cell cytopenia and diminished thymic output, in comparison with that raised against latent, chronic cytomegalovirus (CMV) infection. Serum IgG antibodies anti-spike (S) protein of SARS-CoV-2 and anti-CMV were both determined by chemiluminescent microparticle immunoassays (CMIAs). SARS-CoV-2 and CMV memory CD4+ T-cell responses were simultaneously evaluated in vitro using an activation-induced marker (AIM) assay via multicolor flow cytometry. Throughout the 2-year follow-up that included the administration of five doses of SARS-CoV-2 mRNA vaccines, cellular anti-SARS-CoV-2-specific responses remained consistently negative, with extremely weak humoral responses, while the patient showed in vitro persistent CD4+ T-cell reactivity to CMV peptides and high-IgG CMV-specific titers. The assessment of immune responses to vaccines and prevalent viruses is essential in IEI patients in order to take adequate preventive measures.

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.

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.

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.

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.