Tirofiban versus aspirin to prevent in-stent thrombosis after emergent carotid artery stenting in acute ischemic stroke.

BACKGROUND: Several antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk-benefit is not well known. OBJECTIVE: To investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS. METHODS: We conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250-500 mg single-dose) versus tirofiban (500 µg bolus+200 µg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours. RESULTS: During the period 2019-2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c-3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months. CONCLUSIONS: Periprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

Analysis of losses in physiotherapy students during the COVID-19 pandemic: a phenomenological approach.

BACKGROUND: During the COVID-19 pandemic, young people have experienced numerous personal losses across various aspects, impacting their quality of life. This study aimed to explore and analyze the losses experienced by physiotherapy students during the first year of the COVID-19 pandemic. METHODS: A qualitative phenomenological study was conducted using an open-format exercise carried out during the Clinical Specialties class from February to May 2021. Thirty-four (83% female) third-year physical therapy students participated. ATLAS.ti software was used for the analysis and coding by three researchers. RESULTS: Analysis of the categories revealed various losses experienced by the participants, including losses in psychological well-being, physical health, the social sphere (friendships, relationships with partners and family members, and experiences of death), spiritual losses (loss of freedom and identity), leisure time (travel, recreational activities and physical exercise), and different losses related to university studies (motivation and enthusiasm and clinical practices). CONCLUSION: The COVID-19 pandemic has led to significant losses among physiotherapy students, with losses in the social sphere being the most prevalent. This study can serve as a foundation for developing resources aimed at enhancing the well-being of physiotherapy students, promoting optimal academic performance, improving self-care, and reducing psychosocial problems.

Comprehensive analysis of contaminants in Brazilian infant formulas: Application of QuEChERS coupled with UHPLC-QqQ-MS/MS and suspect screening-unknown analysis by UHPLC-Q-Orbitrap-MS.

Infant formulas (IF) can contain harmful chemical substances, such as pesticides and mycotoxins, resulting from the contamination of raw materials and inputs used in the production chain, which can cause adverse effects to infants. Therefore, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) methodology prior ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ-MS/MS) analysis was applied for the determination of 23 contaminants, in 30 samples of Brazilian IF. The method was validated in terms of limit of detection (0.2 to 0.4 µg/kg), limits of quantification (1 and 10 µg/kg), and recovery (64 % to 122 %); precision values, in terms of relative standard deviation (RSD), were ≤ 20 %. Fenitrothion, chlorpyrifos, and bifenthrin were the pesticides detected in the samples, but the values did not exceed the limit set by the European Union (EU), and ANVISA, and they were detected under their limits of quantification. Additionally, suspect screening and unknown analysis were conducted to tentatively identify 32 substances, including some compounds not covered in this study, such as pesticides, hormones, and veterinary drugs. Carbofuran was identified, confirmed and quantified in 10 % of the samples.

Development of a Risk Prediction Nomogram for Carotid Re-Stenosis in the One Year RECAST Registry.

OBJECTIVE: The long term benefit of carotid angioplasty and stenting (CAS) can be reduced by recurrent stroke related to in stent re-stenosis (ISR). An individualised predictive tool is needed to identify ISR events. A nomogram for individual risk assessment of ISR ≥ 70% after CAS is proposed. METHODS: A national observational, prospective, multicentre registry was conducted between January 2015 and December 2020. Cohorts of patients with symptomatic or asymptomatic severe carotid stenosis who underwent CAS with a follow up of at least one year after CAS were included. Duplex ultrasound was used to assess in stent re-stenosis. Pre-operative factors were compared between the non-ISR and ISR groups. Kaplan-Meier and Cox regression were used for variable selection. The nomogram was formulated and validated by concordance indices and calibration curves. An in stent re-stenosis risk table was generated for risk stratification. RESULTS: A total of 354 patients were included in the analysis. The ISR rate of ≥ 70% was 7.6% (n = 27). Peripheral arterial disease (hazard ratio [HR] 3.18, 95% confidence interval [CI] 1.23 - 8.24, p = .017), anterior communicating artery absence (HR 3.38, 95% CI 1.27 - 8.94, p = .016), diabetes mellitus (HR 3.34, 95% CI 1.21 - 9.26, p = .020), female sex (HR 2.99, 95% CI 1.04 - 8.60, p = .041), and pre-procedure pathological ultrasound vasoreactivity (HR 3.87, 95% CI 1.43 -10.50, p = .008), as independent risk factors for ISR of ≥ 70%, were included in the nomogram. The concordance index at 12 and 24 months was 0.83. In low risk groups, ISR of ≥ 70% occurred in 4.8% of patients during follow up compared with 56.2% of patients in the high risk groups (p < .001). CONCLUSION: The nomogram and risk evaluation score have good predictive ability for ISR. They can be used as practical clinical tools for individualised risk assessment.

Supplementation with a Probiotic Formula Having ß-Glucuronidase Activity Modulates Serum Estrogen Levels in Healthy Peri- and Postmenopausal Women.

Declines in estrogen levels occur in women transitioning to menopause. Estrogen hormones play important roles in multiple systems of the body, and estrogen loss is associated with a variety of symptoms that can decrease quality of life. The gut microbiota is involved in regulating endogenous estrogen levels. A portion of estrogen glucuronides can be reactivated in the gut by the microbial enzyme ß-glucuronidase, and the resulting free estrogens can return to the bloodstream. Here, we carried out in vitro screening of ß-glucuronidase activities for 84 strains belonging to 16 different species of lactic acid bacteria and bifidobacteria and found that one and three strains of Levilactobacillus brevis and Lacticasebacillus rhamnosus, respectively, can deconjugate estrogens. Among these strains, L. brevis KABP052 had the highest ß-glucuronidase activity. Moreover, in an exploratory, randomized, double-blind, placebo-controlled trial, we demonstrated that serum estrogen levels in healthy peri- and postmenopausal women given a probiotic formula containing KABP052 were maintained over time, whereas levels significantly decreased in the group given a placebo. Significantly higher levels of estradiol (31.62 ± 7.97 pg/mL vs. 25.12 ± 8.17 pg/mL) and estrone (21.38 ± 8.57 pg/mL vs. 13.18 ± 8.77 pg/mL) were observed in the probiotic versus placebo group after 12 weeks of intervention. This clinical study demonstrated for the first time the estrogen modulation capacity of a probiotic formula containing a bacterial strain having ß-glucuronidase activity in women during the menopausal transition and formed the basis for future investigations using probiotics in the menopausal population.

Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms.

A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts.

Multiple scale assessment of habitat, landscape, and geographic-specific attributes driving decapod assemblages in Posidonia oceanica seagrass meadows.

Seagrass meadows are biodiversity hotspots for invertebrate species including decapods. Understanding the drivers of species abundance, richness and diversity of decapod assemblages is crucial for the conservation of such hotspots, but how drivers act across multiple spatial scales remains unexplored. Here we describe the decapod assemblages of Posidonia oceanica seagrass meadows and assess the influence of attributes from three increasing spatial scales (habitat, landscape, and geographical levels) on the assemblages' structure and composition, as well as the variability partitioning among each one of these levels. Overall, geographical level attributes (i.e., inlet aperture, confinement) affected the most the decapod assemblages, while we only found a modest contribution from habitat (e.g., detritus biomass, sediment organic matter) and landscape attributes (e.g., fragmentation). We suggest that decapod assemblages are driven by the interaction of multiple processes occurring at different scales and other highly stochastic phenomena such as larval dispersion and recruitment.

SwissDock 2024: major enhancements for small-molecule docking with Attracting Cavities and AutoDock Vina.

Drug discovery aims to identify potential therapeutic compounds capable of modulating the activity of specific biological targets. Molecular docking can efficiently support this process by predicting binding interactions between small molecules and macromolecular targets and potentially accelerating screening campaigns. SwissDock is a computational tool released in 2011 as part of the SwissDrugDesign project, providing a free web-based service for small-molecule docking after automatized preparation of ligands and targets. Here, we present the latest version of SwissDock, in which EADock DSS has been replaced by two state-of-the-art docking programs, i.e. Attracting Cavities and AutoDock Vina. AutoDock Vina provides faster docking predictions, while Attracting Cavities offers more accurate results. Ligands can be imported in various ways, including as files, SMILES notation or molecular sketches. Targets can be imported as PDB files or identified by their PDB ID. In addition, advanced search options are available both for ligands and targets, giving users automatized access to widely-used databases. The web interface has been completely redesigned for interactive submission and analysis of docking results. Moreover, we developed a user-friendly command-line access which, in addition to all options of the web site, also enables covalent ligand docking with Attracting Cavities. The new version of SwissDock is freely available at https://www.swissdock.ch/.

Aethionema arabicum dimorphic seed trait resetting during transition to seedlings.

The transition from germinating seeds to emerging seedlings is one of the most vulnerable plant life cycle stages. Heteromorphic diaspores (seed and fruit dispersal units) are an adaptive bet-hedging strategy to cope with spatiotemporally variable environments. While the roles and mechanisms of seedling traits have been studied in monomorphic species, which produce one type of diaspore, very little is known about seedlings in heteromorphic species. Using the dimorphic diaspore model Aethionema arabicum (Brassicaceae), we identified contrasting mechanisms in the germination responses to different temperatures of the mucilaginous seeds (M+ seed morphs), the dispersed indehiscent fruits (IND fruit morphs), and the bare non-mucilaginous M- seeds obtained from IND fruits by pericarp (fruit coat) removal. What follows the completion of germination is the pre-emergence seedling growth phase, which we investigated by comparative growth assays of early seedlings derived from the M+ seeds, bare M- seeds, and IND fruits. The dimorphic seedlings derived from M+ and M- seeds did not differ in their responses to ambient temperature and water potential. The phenotype of seedlings derived from IND fruits differed in that they had bent hypocotyls and their shoot and root growth was slower, but the biomechanical hypocotyl properties of 15-day-old seedlings did not differ between seedlings derived from germinated M+ seeds, M- seeds, or IND fruits. Comparison of the transcriptomes of the natural dimorphic diaspores, M+ seeds and IND fruits, identified 2,682 differentially expressed genes (DEGs) during late germination. During the subsequent 3 days of seedling pre-emergence growth, the number of DEGs was reduced 10-fold to 277 root DEGs and 16-fold to 164 shoot DEGs. Among the DEGs in early seedlings were hormonal regulators, in particular for auxin, ethylene, and gibberellins. Furthermore, DEGs were identified for water and ion transporters, nitrate transporter and assimilation enzymes, and cell wall remodeling protein genes encoding enzymes targeting xyloglucan and pectin. We conclude that the transcriptomes of seedlings derived from the dimorphic diaspores, M+ seeds and IND fruits, undergo transcriptional resetting during the post-germination pre-emergence growth transition phase from germinated diaspores to growing seedlings.

Postural Control and Sensory Processing in Preschool Children with Autistic Spectrum Disorder: A Cross-Sectional Study.

The role of sensory processing in maintaining postural control (PC) among preschool-aged children with autism spectrum disorder (ASD) remains underexplored despite its potential implications for their developmental trajectory. This study aimed to assess the utilization of sensory information for PC maintenance while standing in preschool-aged children with ASD and to examine its correlation with PC during functional tasks using a standardized tool. The cross-sectional study recruited 27 children, aged between 3 and 6 years, diagnosed with ASD. Participation indexes for somatosensory, vestibular, visual, and visual preference were computed during a modified Clinical Test of Sensory Integration and Balance (m-CTSIB), based on sagittal plane body sway analyzed via video with Kinovea® software (version 0.9.4). Additionally, scores from the Pediatric Balance Scale (PBS) were analyzed. Statistical analysis of data derived from lateral malleolus and mastoid process sway using the Friedman test revealed significant differences in the utilization of various sensory systems involved in PC during the m-CTSIB (p < 0.001). There was a pronounced reliance on somatosensory information, coupled with increased instability in the absence or with the variability of visual information. The mean PBS score was 50.44 ± 2.74, exhibiting a significant negative correlation with the vestibular index (p < 0.05). Preschool-aged children with ASD demonstrated challenges in maintaining PC while standing under different sensory conditions, indicating a heightened dependence on somatosensory cues, particularly in the absence or with the variability of visual stimuli. While these challenges were not reflected in PBS scores, they were negatively correlated with the vestibular index.

Refining risk prediction in pediatric acute lymphoblastic leukemia through DNA methylation profiling.

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, and despite considerable progress in treatment outcomes, relapses still pose significant risks of mortality and long-term complications. To address this challenge, we employed a supervised machine learning technique, specifically random survival forests, to predict the risk of relapse and mortality using array-based DNA methylation data from a cohort of 763 pediatric ALL patients treated in Nordic countries. The relapse risk predictor (RRP) was constructed based on 16 CpG sites, demonstrating c-indexes of 0.667 and 0.677 in the training and test sets, respectively. The mortality risk predictor (MRP), comprising 53 CpG sites, exhibited c-indexes of 0.751 and 0.754 in the training and test sets, respectively. To validate the prognostic value of the predictors, we further analyzed two independent cohorts of Canadian (n = 42) and Nordic (n = 384) ALL patients. The external validation confirmed our findings, with the RRP achieving a c-index of 0.667 in the Canadian cohort, and the RRP and MRP achieving c-indexes of 0.529 and 0.621, respectively, in an independent Nordic cohort. The precision of the RRP and MRP models improved when incorporating traditional risk group data, underscoring the potential for synergistic integration of clinical prognostic factors. The MRP model also enabled the definition of a risk group with high rates of relapse and mortality. Our results demonstrate the potential of DNA methylation as a prognostic factor and a tool to refine risk stratification in pediatric ALL. This may lead to personalized treatment strategies based on epigenetic profiling.

Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects.

Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Mannheimia haemolytica-associated fibrinonecrotizing abomasitis in lambs.

Mannheimia haemolytica-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a severe fibrinonecrotizing abomasitis in 3 lambs that died suddenly. All 3 abomasums had a thickened submucosa due to edema and necrotic areas delimited by bands of degenerate neutrophils with slender nuclei (oat cells) and angiocentric distributions. The overlying mucosa was congested. Myriads of gram-negative coccobacilli were observed within the oat cell bands. M. haemolytica was isolated from the abomasum in all 3 animals and was serotyped as A2 in one of them. Pericarditis and pleuritis were observed in 2 of the lambs. Clostridium spp. were isolated in 1 lamb and detected by immunohistochemistry in the 3 animals, suggesting clostridial co-infection. M. haemolytica should be considered among the differential diagnoses of necrotizing abomasitis in lambs.

[Advance care planning in nursing homes: scoping review]. / Planificación anticipada de cuidados en residencias de mayores: revisión narrativa.

Advance care planning is a deliberative process that aims to help patients define goals and preferences for future care and treatment at a times when they have limited decision-making capacity. This study aims to analyze models of advance care planning in elderly individuals living in nursing homes. We reviewed papers published in Cochrane, PubMed and Embase. A total of 26 studies were selected, including a total of 44,131 people over 65 years of age. We analyzed the types of intervention (interviews, videos, workshops, documentation, etc.) and their results derived from the application. We conclude that no study implements a standardized intervention model. These interventions include decision-making (transfers to hospital, resucitation orders) and the adequacy of therapeutic effort (antibiotherapy, nutrition, serotherapy, etc.). Other outcomes are implementation barriers (time and training).

Risk Factors for Multiple Violations of Protective Orders in Intimate Partner Violence Against Women.

This study examined 1,134 cases of violence against women in intimate partner relationships with violations of protective orders in a monitoring period of up to 15 months. The dynamics of time and violence were analyzed in the cases of multiple violation versus one-time violation, with the objective of identifying and thus neutralizing the risk factors for this type of recidivism. The results showed that early violation, serious physical violence, death threats, as well as jealousy, harassment, and control are related to multiple violation. This article discusses the results in comparison with other research and proposes measures to avoid revictimizations.

The dimorphic diaspore model Aethionema arabicum (Brassicaceae): Distinct molecular and morphological control of responses to parental and germination temperatures.

Plants in habitats with unpredictable conditions often have diversified bet-hedging strategies that ensure fitness over a wider range of variable environmental factors. A striking example is the diaspore (seed and fruit) heteromorphism that evolved to maximize species survival in Aethionema arabicum (Brassicaceae) in which external and endogenous triggers allow the production of two distinct diaspores on the same plant. Using this dimorphic diaspore model, we identified contrasting molecular, biophysical, and ecophysiological mechanisms in the germination responses to different temperatures of the mucilaginous seeds (M+ seed morphs), the dispersed indehiscent fruits (IND fruit morphs), and the bare non-mucilaginous M- seeds obtained by pericarp (fruit coat) removal from IND fruits. Large-scale comparative transcriptome and hormone analyses of M+ seeds, IND fruits, and M- seeds provided comprehensive datasets for their distinct thermal responses. Morph-specific differences in co-expressed gene modules in seeds, as well as in seed and pericarp hormone contents, identified a role of the IND pericarp in imposing coat dormancy by generating hypoxia affecting abscisic acid (ABA) sensitivity. This involved expression of morph-specific transcription factors, hypoxia response, and cell wall remodeling genes, as well as altered ABA metabolism, transport, and signaling. Parental temperature affected ABA contents and ABA-related gene expression and altered IND pericarp biomechanical properties. Elucidating the molecular framework underlying the diaspore heteromorphism can provide insight into developmental responses to globally changing temperatures.

Transcriptomic analysis of turbot (Scophthalmus maximus) treated with zymosan a reveals that lncRNAs and inflammation-related genes mediate the protection conferred against Aeromonas salmonicida.

Aeromonas salmonicida is one of the most harmful pathogens in finfish aquaculture worldwide. Immunostimulants such as ß-glucans are used to enhance the immunity of cultured fish. However, their effects on fish physiology are not completely understood. In the present work, we evaluated the effect of a single intraperitoneal (ip) injection of zymosan A on fish survival against A. salmonicida infection. A single administration of this compound protected fish against A. salmonicida challenge and reduce the bacterial load in the head kidney one week after its administration. Transcriptome analyses of head kidney samples revealed several molecular mechanisms involved in the protection conferred by zymosan A and their regulation by long noncoding RNAs. The transcriptome profile of turbot exposed only to zymosan A was practically unaltered one week after ip injection. However, the administration of this immunostimulant induced significant transcriptomic changes once the fish were in contact with the bacteria and increased the survival of the infected turbot. Our results suggest that the restraint of the infection-induced inflammatory response, the management of apoptotic cell death, cell plasticity and cellular processes involving cytoskeleton dynamics support the protective effects of zymosan A. All this information provides insights on the cellular and molecular mechanisms involved in the protective effects of this widely used immunostimulant.

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.