Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

Hidden impacts of ocean warming and acidification on biological responses of marine animals revealed through meta-analysis.

Conflicting results remain on the impacts of climate change on marine organisms, hindering our capacity to predict the future state of marine ecosystems. To account for species-specific responses and for the ambiguous relation of most metrics to fitness, we develop a meta-analytical approach based on the deviation of responses from reference values (absolute change) to complement meta-analyses of directional (relative) changes in responses. Using this approach, we evaluate responses of fish and invertebrates to warming and acidification. We find that climate drivers induce directional changes in calcification, survival, and metabolism, and significant deviations in twice as many biological responses, including physiology, reproduction, behavior, and development. Widespread deviations of responses are detected even under moderate intensity levels of warming and acidification, while directional changes are mostly limited to more severe intensity levels. Because such deviations may result in ecological shifts impacting ecosystem structures and processes, our results suggest that climate change will likely have stronger impacts than those previously predicted based on directional changes alone.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations.

Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more efficiently than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to those of NTV. A crucial feature of ML2006a4 is a derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Last, ML2006a4 was found to be less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory design can preemptively address potential resistance mechanisms to expand future treatment options against coronavirus variants.

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.

Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

Structural insights reveal interplay between LAG-3 homodimerization, ligand binding, and function.

Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function. Additionally, we found a previously unidentified key protein-glycan interaction in the dimer interface that affects the spatial orientation of the neighboring D1 domain. Mutation of LAG-3 D2 residues reduced dimer formation, dramatically abolished LAG-3 binding to both MHCII and FGL1 ligands, and consequentially inhibited the role of LAG-3 in suppressing T cell responses. Intriguingly, we showed that antibodies directed against D1, D2, and D3 domains are all capable of blocking LAG-3 dimer formation and MHCII and FGL-1 ligand binding, suggesting a potential allosteric model of LAG-3 function tightly regulated by dimerization. Furthermore, our work reveals unique epitopes, in addition to D1, that can be targeted for immunotherapy of cancer and other human diseases.

Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

Ketamine in the treatment of refractory and super-refractory status epilepticus: Experience from two centres.

PURPOSE: There is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. METHODS: Adult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. RESULTS: This study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. CONCLUSION: Ketamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.

Development and Psychometric Validation of the Breast Cancer Stigma Assessment Scale for Women with Breast Cancer and Its Survivors.

BACKGROUND: The increase in breast cancer cases and breast cancer survival makes it advisable to quantify the impact of the health-related stigma of this disease. PURPOSE/OBJECTIVES: To develop and validate a breast cancer stigma scale in Spanish. METHODS: Women diagnosed with, or survivors of, breast cancer were included. The development of the Breast Cancer Stigma Assessment Scale (BCSAS) involved both a literature review and personal interviews. Content validity was assessed using a Delphi study and a pilot test; construct validity was evaluated using an exploratory factor analysis; and convergent validity was assessed using six scales. Cronbach's α internal consistency and test-retest reliability were used to determine the reliability of the scales. RESULTS: 231 women responded to the 28-item scale. The BCSAS showed good reliability, with α = 0.897. Seven factors emerged: concealment (α = 0.765), disturbance (α = 0.772), internalized stigma (α = 0.750), aesthetics (α = 0.779), course (α = 0.599), danger (α = 0.502), and origin (α = 0.350). The test-retest reliability was 0.830 (p < 0.001). Significant correlation was observed with event centrality (r = 0.701), anxiety-depression (r = 0.668), shame (r = 0.645), guilt (r = 0.524), and quality of life (r = -0.545). CONCLUSIONS: The BCSAS is a reliable and valid measure of stigma in women with breast cancer and its survivors. It could be useful for detecting stigma risk and establishing psychotherapeutic and care priorities.

Clinical Simulation in Palliative Care for Undergraduate Nursing Students: A Randomized Clinical Trial and Complementary Qualitative Study.

BACKGROUND: a lack of adequate training in palliative care leads to a greater emotional burden on nurses. PURPOSE: to assess the effect of a simulation using standardized patients on self-efficacy in palliative care, ability to cope with death, and emotional intelligence among nursing students. METHODS: a randomized clinical trial and qualitative study. A total of 264 nursing students in a palliative care module completed the Bugen, trait meta-mood, and self-efficacy in palliative care scales after active participation in the simulation (n = 51), watching the simulation (n = 113), and the control group (n = 100). An ANOVA with a multi-comparative analysis and McNemar's tests for paired samples were calculated. Active participants were interviewed, and a thematic analysis was conducted. RESULTS: there was an improvement after the assessment in all three groups assessed for coping with death (p < 0.01), emotional intelligence (p < 0.01), and self-efficacy (p < 0.01). In addition, the active group improved more than the observer group and the control group in coping with death, attention, and repair. The students in the interviews identified sadness and an emotional lack of control. CONCLUSIONS: the simulation improved nursing students' self-efficacy in palliative care. This effect was partially stronger in the active group.

Exploring the Implementation of GaAsBi Alloys as Strain-Reducing Layers in InAs/GaAs Quantum Dots.

This paper investigates the effect of GaAsBi strain reduction layers (SRLs) on InAs QDs with different Bi fluxes to achieve nanostructures with improved temperature stability. The SRLs are grown at a lower temperature (370 °C) than the usual capping temperature for InAs QDs (510 °C). The study finds that GaAs capping at low temperatures reduces QD decomposition and leads to larger pyramidal dots but also increases the threading dislocation (TD) density. When adding Bi to the capping layer, a significant reduction in TD density is observed, but unexpected structural changes also occur. Increasing the Bi flux does not increase the Bi content but rather the layer thickness. The maximum Bi content for all layers is 2.4%. A higher Bi flux causes earlier Bi incorporation, along with the formation of an additional InGaAs layer above the GaAsBi layer due to In segregation from QD erosion. Additionally, the implementation of GaAsBi SRLs results in smaller dots due to enhanced QD decomposition, which is contrary to the expected function of an SRL. No droplets were detected on the surface of any sample, but we did observe regions of horizontal nanowires within the epilayers for the Bi-rich samples, indicating nanoparticle formation.

Weighting Low-Intensity MS/MS Ions and m/z Frequency for Spectral Library Annotation.

Calculating spectral similarity is a fundamental step in MS/MS data analysis in untargeted metabolomics experiments, as it facilitates the identification of related spectra and the annotation of compounds. To improve matching accuracy when querying an experimental mass spectrum against a spectral library, previous approaches have proposed increasing peak intensities for high m/z ranges. These high m/z values tend to be smaller in magnitude, yet they offer more crucial information for identifying the chemical structure. Here, we evaluate the impact of using these weights for identifying structurally related compounds and mass spectral library searches. Additionally, we propose a weighting approach that (i) takes into account the frequency of the m/z values within a spectral library in order to assign higher importance to the most common peaks and (ii) increases the intensity of lower peaks, similar to previous approaches. To demonstrate our approach, we applied weighting preprocessing to modified cosine, entropy, and fidelity distance metrics and benchmarked it against previously reported weights. Our results demonstrate how weighting-based preprocessing can assist in annotating the structure of unknown spectra as well as identifying structurally similar compounds. Finally, we examined scenarios in which the utilization of weights resulted in diminished performance, pinpointing spectral features where the application of weights might be detrimental.

Transparency as a Means to Analyse the Impact of Inertial Sensors on Users during the Occupational Ergonomic Assessment: A Systematic Review.

The literature has yielded promising data over the past decade regarding the use of inertial sensors for the analysis of occupational ergonomics. However, despite their significant advantages (e.g., portability, lightness, low cost, etc.), their widespread implementation in the actual workplace has not yet been realized, possibly due to their discomfort or potential alteration of the worker's behaviour. This systematic review has two main objectives: (i) to synthesize and evaluate studies that have employed inertial sensors in ergonomic analysis based on the RULA method; and (ii) to propose an evaluation system for the transparency of this technology to the user as a potential factor that could influence the behaviour and/or movements of the worker. A search was conducted on the Web of Science and Scopus databases. The studies were summarized and categorized based on the type of industry, objective, type and number of sensors used, body parts analysed, combination (or not) with other technologies, real or controlled environment, and transparency. A total of 17 studies were included in this review. The Xsens MVN system was the most widely used in this review, and the majority of studies were classified with a moderate level of transparency. It is noteworthy, however, that there is a limited and worrisome number of studies conducted in uncontrolled real environments.

Free PCR virus detection via few-layer bismuthene and tetrahedral DNA nanostructured assemblies.

In this work we describe a highly sensitive method based on a biocatalyzed electrochemiluminescence approach. The system combines, for the first time, the use of few-layer bismuthene (FLB) as a platform for the oriented immobilization of tetrahedral DNA nanostructures (TDNs) specifically designed and synthetized to detect a specific SARS-CoV-2 gene sequence. In one of its vertices, these TDNs contain a DNA capture probe of the open reading frame 1 ab (ORF1ab) of the virus, available for the biorecognition of the target DNA/RNA. At the other three vertices, there are thiol groups that enable the stable anchoring/binding to the FLB surface. This novel geometry/approach enables not only the binding of the TDNs to surfaces, but also the orientation of the capture probe in a direction normal to the bismuthine surface so that it is readily accessible for binding/recognition of the specific SARS-CoV-2 sequence. The analytical signal is based on the anodic electrochemiluminescence (ECL) intensity of luminol which, in turn, arises as a result of the reaction with H2O2, generated by the enzymatic reaction of glucose oxidation, catalyzed by the biocatalytic label avidin-glucose oxidase conjugate (Av-GOx), which acts as co-reactant in the electrochemiluminescent reaction. The method exhibits a limit of detection (LOD) of 4.31 aM and a wide linear range from 14.4 aM to 1.00 µM, and its applicability was confirmed by detecting SARS-CoV-2 in nasopharyngeal samples from COVID-19 patients without the need of any amplification process.

Attitudes and experiences related to the deaths of COVID-19 patients among nursing staff: A qualitative evidence synthesis.

AIM: To identify and synthesize the experiences and attitudes of nursing staff regarding the deaths of COVID-19 patients. REVIEW METHODS: A qualitative evidence synthesis was carried out, using Noblit and Hare's meta-ethnographic approach. The review protocol was listed in PROSPERO (CRD42022330928). Studies published from January 2020 to January 2022 that met the criteria were searched in PubMed, Web of Science, Scopus, CINAHL, CUIDEN and PsycInfo. A total of 12 articles were included. RESULTS: Thirty-three metaphors emerged, which were grouped into three main themes: Determining factors of care, Feelings about death and Strategies for coping with death. Nurses reported the high emotional toll, the absence of family and the lack of staff, protocol and training as determining factors. Furthermore, staff had doubts about the quality of care that COVID-19 patients received. As coping strategies, nurses developed avoidance behaviours towards COVID-19 patients, selective memories, resilience, and/or leaving the profession. CONCLUSIONS: The difficulty in providing adequate nursing care and the high number of deaths has increased anxiety and stress among nurses. These factors, alongside their lived experiences of seeing patients suffering, many dying alone without family members, have had psychological repercussions on nursing staff. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The results demonstrate a high emotional toll and doubts surrounding their caregiving role caused by the lack of professional training needed to face a pandemic. This research shows what has been learned for future pandemics and highlights basic components that could provide a foundation for coping interventions for healthcare professionals. IMPACT: WHAT PROBLEM DID THE STUDY ADDRESS?: The challenges posed by COVID-19 patient deaths for nursing staff around the world and also by the pandemic circumstances in which those deaths occurred. WHAT WERE THE MAIN FINDINGS?: The high number of deceased patients who were isolated from family members, communication with family members and doubts surrounding care given during the pandemic have created feelings of fear, stress and anxiety, as well as obsessive thoughts that have changed nursing staff's perception of death due to COVID-19. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: Results will be useful for preparing for future pandemics, and for policymakers and health staff in supporting healthcare professionals by creating programmes to help them cope with the emotional toll they have felt after dealing with death in such unprecedented circumstances. REPORTING METHOD: The authors have adhered to the PRISMA guidelines and the eMERGe Reporting Guidance. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A new fluorescent probe for the visualization of progerin.

Hutchinson-Gilford progeria syndrome (HGPS) or progeria is a rare genetic disease that causes premature aging, leading to a drastic reduction in the life expectancy of patients. Progeria is mainly caused by the intracellular accumulation of a defective protein called progerin, generated from a mutation in the LMNA gene. Currently, there is only one approved drug for the treatment of progeria, which has limited efficacy. It is believed that progerin levels are the most important biomarker related to the severity of the disease. However, there is a lack of effective tools to directly visualize progerin in the native cellular models, since the commercially available antibodies are not well suited for the direct visualization of progerin in cells from the mouse model of the disease. In this context, an alternative option for the visualization of a protein relies on the use of fluorescent chemical probes, molecules with affinity and specificity towards a protein. In this work we report the synthesis and characterization of a new fluorescent probe (UCM-23079) that allows for the direct visualization of progerin in cells from the most widely used progeroid mouse model. Thus, UCM-23079 is a new tool compound that could help prioritize potential preclinical therapies towards the final goal of finding a definitive cure for progeria.

A "signal off-on" fluorescence bioassay based on 2D-MoS2-tetrahedral DNA bioconjugate for rapid virus detection.

In this work we present the preparation of a 2D molybdenum disulphide nanosheets (2D-MoS2) and tetrahedral DNA nanostructures (TDNs) bioconjugate, and its application to the development of a bioassay for rapid and easy virus detection. The bioconjugate has been prepared by using TDNs carrying the capture probe labelled with 6-carboxyfluoresceine (6-FAM). As case of study to assess the utility of the assay developed, we have chosen the SARS-CoV-2 virus. Hence, as probe we have used a DNA sequence complementary to a region of the SARS-CoV-2 ORF1ab gene (TDN-ORF-FAM). This 6-FAM labelled capture probe is located on the top vertex of the tetrahedral DNA nanostructure, the three left vertices of TDNs have a thiol group. These TDNs are bounded to 2D-MoS2 surface through the three thiol groups, allowing the capture probe to be oriented to favour the biorecognition reaction with the analyte. This biorecognition resulting platform has finally been challenged to the detection of the SARS-CoV-2 ORF1ab gene sequence as the target model by measuring fluorescence before and after the hybridization event with a detection limit of 19.7fM. Furthermore, due to high sensitivity of the proposed methodology, it has been applied to directly detect the virus in nasopharyngeal samples of infected patients without the need of any amplification step. The developed bioassay has a wide range of applicability since it can be applied to the detection of any pathogen by changing the probe corresponding to the target sequence. Thus, a novel, hands-on strategy for rapid pathogen detection has proposed and has a high potential application value in the early diagnosis of infections causes by virus or bacteria.

Coinfección bacteriana en el paciente COVID-19 crítico: incidencia, impacto y necesidad de tratamiento antibiótico / Bacterial coinfection in the critically-ill COVID-19 patient: incidence, impact and need for antimicrobial therapy

Objetivos. Evaluar la frecuencia de coinfección bacteriana al ingreso en UCI en pacientes con neumonía por SARS-CoV-2, su microbiología e impacto en el pronóstico. El objetivo secun dario fue identificar factores de riesgo de coinfección al ingreso. Métodos. Estudio retrospectivo, se incluyeron pacientes con neumonía por SARS-CoV-2 ingresados en UCI. Definimos coinfección bacteriana por síntomas respiratorios, datos radioló gicos, resultados microbiológicos positivos y clínicamente signi ficativos en muestras obtenidas en las primeras 48 h de ingreso y/o una determinación de procalcitonina ≥ 0,5 ng/mL en las pri meras 48 h. Evaluamos variables demográficas, comorbilidades, datos de la infección por SARS-CoV-2, scores de gravedad, tra tamientos recibidos, necesidad de soporte respiratorio y resulta dos (estancia y mortalidad durante el ingreso en UCI y hospital). Resultados. Se analizaron 182 pacientes, 62 (34.1%) con coinfección bacteriana. La microbiología más frecuente fue S. pneumoniae y M. pneumoniae. El 96.1% de los pacientes re cibieron antibioterapia al ingreso, 98,9% corticoides, 27,5% tocilizumab y 7,7% remdesivir. El 85.7% necesitó ventilación mecánica invasiva. La puntuación en SOFA (OR: 1,315, IC 95% 1,116-1,548) y el retraso en el ingreso en UCI (OR: 0,899, IC 95% 0,831-0,972) se relacionaron con el riesgo de coinfección. La coinfección bacteriana aumenta el riesgo de muerte en el hospital (OR 2,283; IC 95% 1,011-5,151; p=0,047). Conclusiones. La coinfección bacteriana es frecuente en pacientes COVID ingresados en UCI y aumenta el riesgo de muerte. No es posible identificar con seguridad, en el momen to de ingreso, qué pacientes no se benefician de tratamiento antibiótico (AU)

ion upon ICU admission in SARS-CoV-2 pneumonia patients, its microbiology, and impact on prognosis.The secondary ob jective was to identify risk factors for coinfection on admis sion. Methods. Retrospective study, including patients with SARS-CoV-2 pneumonia admitted to the ICU.We defined bac terial coinfection by respiratory symptoms, radiological data, positive and clinically significant microbiological results in samples obtained in the first 48 h of admission and/or a de termination of procalcitonin ≥ 0.5 ng/mL in the first 48 h.We evaluated demographic variables, comorbidities, SARS-CoV-2 infection data, severity scores, treatments received, need for respiratory support and outcomes (ICU and hospital mortality). Results. A total of 182 patients were analyzed, 62 (34.1%) with bacterial coinfection.The most frequent microbiology was S. pneumoniae and M. pneumoniae.96.1% of the patients re ceived antibiotic therapy on admission, 98.9% corticosteroids, 27.5% tocilizumab, and 7.7% remdesivir.85.7% required inva sive mechanical ventilation.The SOFA score (OR: 1.315, 95% CI 1.116-1.548) and the delay in ICU admission (OR: 0.899, 95% CI 0.831-0.972) were related to the risk of coinfection.Bacterial coinfection increases the risk of death in hospital (OR 2.283; 95% CI 1.011.5.151; p=0.047). Conclusions. Bacterial coinfection is common in COVID patients admitted to the ICU and increases the risk of death.It is not possible to identify with certainty, at the time of admis sion, which patients do not benefit from antibiotic treatment (AU)

Predictive factors of the psychological impact of the COVID-19 pandemic on university students: a study in six Ibero-American countries / Factores predictivos del impacto psicológico de la pandemia de COVID-19 en estudiantes universitarios: un estudio en seis países iberoamericanos

Background/Objective: During Covid-19, high prevalences of anxiety and depression were reported among university students, suggesting that they may be at higher risk than the general population of developing psychological disorders in lockdown situations. This study aimed to analyze how sociocultural factors and individual differences contributed to explaining the psychological impact of the pandemic among Ibero-American university students from Argentina, Colombia, Ecuador, Spain, Mexico, and Uruguay. Method: The study was carried out on 7601 university students (72% women). Data were collected through an online questionnaire that measured anxiety (GAD-2), depression (PHQ-2), somatic symptoms (SSQ-5), post-traumatic growth (PTGI), loneliness (UCLS), personality (NEO-FFI), Resilience (CD-RISC-2), Perceived Competences (PCS) and sociodemographic data. Descriptive statistics and multiple linear regression model were performed. Results: Analysis indicated a high prevalence (46.15%) of distress among university students, regardless of country and significantly higher than in the general population (28.27%). Greater feelings of loneliness and greater neuroticism were significantly associated with anxiety, depression, and somatization. Likewise, male gender and higher levels of resilience were found to be protective factors, while post-traumatic growth was also higher in men and was associated with higher levels of resilience, perceived competence, and responsibility. Conclusions: The results suggest the need to consider individual risk factors such as being a woman, presenting higher levels of neuroticism and loneliness in understanding the psychological impact of the pandemic on university students. It is concluded that universities should offer specific interventions to address mental health problems and manage the added complications of crisis events on the health of students.(AU)

Antecedentes/Objetivo: Durante el Covid-19, se informaron altas prevalencias de ansiedad y depresión entre estudiantes universitarios, lo que sugiere que pueden tener un mayor riesgo que la población general de desarrollar trastornos psicológicos en situaciones de encierro. Este estudio tuvo como objetivo analizar cómo los factores socioculturales y las diferencias individuales contribuyeron a explicar el impacto psicológico de la pandemia entre estudiantes universitarios iberoamericanos de Argentina, Colombia, Ecuador, España, México y Uruguay. Método: El estudio se realizó en 7601 estudiantes universitarios (72% mujeres). Los datos fueron recolectados a través de un cuestionario en línea que midió ansiedad (GAD-2), depresión (PHQ-2), síntomas somáticos (SSQ-5), crecimiento postraumático (PTGI), soledad (UCLS), personalidad (NEO-FFI), Resiliencia (CD-RISC-2), Competencia Percibida (PCS) y datos sociodemográficos. Se realizó estadística descriptiva y modelo de regresión lineal múltiple. Resultados: Los análisis indicaron una alta prevalencia (46,15%) de angustia entre los estudiantes universitarios, independientemente del país y significativamente mayor que en la población general (28,27%). Mayores sentimientos de soledad y mayor neuroticismo se asociaron significativamente con ansiedad, depresión y somatización. Asimismo, el género masculino y mayores niveles de resiliencia resultaron ser factores protectores, mientras que el crecimiento postraumático también fue mayor en los hombres y se asoció con mayores niveles de resiliencia, competencia percibida y responsabilidad. Conclusiones: Los resultados sugieren la necesidad de considerar factores de riesgo individuales como ser mujer, presentar mayores niveles de neuroticismo y soledad en la comprensión del impacto psicológico de la pandemia en estudiantes universitarios. Se concluye que las universidades deben ofrecer intervenciones específicas para abordar los problemas de salud mental y manejar las complicaciones añadidas de los eventos de crisis sobre la salud de los estudiantes.(AU)

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score.

BACKGROUND: The risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. METHODS: The study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. RESULTS: We included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE. A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13-4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03-4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07-3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40-5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3-84.3 %, p < 0.001). CONCLUSIONS: The AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.