Dissemination of antimicrobial resistance in agricultural ecosystems following irrigation with treated municipal wastewater.

The spread of antimicrobial resistance (AMR) in agricultural systems via irrigation water is a serious public health issue as it can be transmitted to humans through the food chain. Therefore, understanding the dissemination routes of antibiotic resistance genes (ARGs) in agricultural systems is crucial for the assessment of health risks associated with eating fresh vegetables such as spinach and radish irrigated with treated municipal wastewater (TMW). In this study, we investigated the bacterial community structure and resistome in the soil-plant-earthworm continuum after irrigation of spinach and radish with TMW containing the antibiotics trimethoprim (TMP), sulfamethoxazole (SMZ), and sulfapyridine (SPD) using 16S rRNA gene sequencing and high throughput quantitative PCR (HT-qPCR). The study was conducted in two phases: Phase I involved eight weeks of spinach and radish production using TMW for irrigation, whereas Phase II entailed three weeks of earthworm exposure to contaminated plant material obtained in Phase I. The 16S data indicated that the rhizosphere bacterial community composition and structure were more resilient to antibiotic residuals in the irrigated water, with radish showing less susceptibility than spinach than those of bulk soils. The HT-qPCR analysis revealed that a total of 271 ARGs (out of 285) and 9 mobile genetic elements (MGEs) (out of 10) were detected in all samples. Higher diversity and abundance of ARGs were observed for samples irrigated with higher concentrations of antibiotics in both spinach and radish treatments. However, compared to spinach, radish ARG dynamics in the soil biome were more stable due to the change of antibiotic introduction to the soil. At the class level, multi-drug resistance (MDR) class was altered significantly by the presence of antibiotics in irrigation water. Compared to earthworm fecal samples, their corresponding soil environments showed a higher number of detected ARGs, suggesting that earthworms could play a role in reducing ARG dissemination in the soil environments. These findings will not only provide insight into the dissemination of ARGs in agricultural environments due to antibiotic residuals in irrigated water but could help understand the potential human health risks associated with ARGs.

Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries.

Spinal cord injury (SCI) represents a severe trauma to the nervous system, leading to significant neurological damage, chronic inflammation, and persistent neuropathic pain. Current treatments, including pharmacotherapy, immobilization, physical therapy, and surgical interventions, often fall short in fully addressing the underlying pathophysiology and resultant disabilities. Emerging research in the field of regenerative medicine has introduced innovative approaches such as autologous orthobiologic therapies, with bone marrow aspirate (BMA) being particularly notable for its regenerative and anti-inflammatory properties. This review focuses on the potential of BMA to modulate inflammatory pathways, enhance tissue regeneration, and restore neurological function disrupted by SCI. We hypothesize that BMA's bioactive components may stimulate reparative processes at the cellular level, particularly when applied at strategic sites like the sacral hiatus to influence lumbar centers and higher neurological structures. By exploring the mechanisms through which BMA influences spinal repair, this review aims to establish a foundation for its application in clinical settings, potentially offering a transformative approach to SCI management that extends beyond symptomatic relief to promoting functional recovery.

Cohort Profile: the European Unified Registries On Heart care Evaluation and Randomised Trials (EuroHeart) - Acute Coronary Syndrome and Percutaneous Coronary Intervention.

AIMS: The European Unified Registries On Heart care Evaluation And Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries. METHODS AND RESULTS: Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting.Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women. CONCLUSION: The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.

Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Outcomes of ventricular tachycardia ablation in patients with ischemic and non-ischemic cardiomyopathy: A propensity-score matched analysis.

INTRODUCTION AND OBJECTIVES: Catheter ablation (CA) is effective in the treatment of ventricular tachycardia (VT). Although some observational data suggest patients with non-ischemic cardiomyopathy (NICM) have less favorable outcomes when compared to those with an ischemic etiology (ICM), direct comparisons are rarely reported. We aimed to compare the outcomes of VT ablation in a propensity-score matched population of ICM or NICM patients. METHODS: Single-center retrospective study of consecutive patients undergoing VT ablation from 2012 to 2023. A propensity score (PS) was used to match ICM and NICM patients in a 1:1 fashion according to age, sex, left ventricular ejection fraction (LVEF), NYHA class, electrical storm (ES) at presentation, and previous endocardial ablation. The outcomes of interest were VT-free survival and all-cause mortality. RESULTS: The PS yielded two groups of 71 patients each (mean age 63±10 years, 92% male, mean LVEF 35±10%, 36% with ES at presentation, and 23% with previous ablation), well matched for baseline characteristics. During a median follow-up of 2.3 (interquartile range IQR 1.3-3.8) years, patients with NICM had a significantly lower VT-free survival (53.5% vs. 69.0%, log-rank p=0.037), although there were no differences regarding all-cause mortality (22.5% vs. 16.9%, log-rank p=0.245). Multivariate analysis identified NICM (HR 2.34 [95% CI 1.32-4.14], p=0.004), NYHA class III/IV (HR 2.11 [95% CI 1.11-4.04], p=0.024), and chronic kidney disease (HR 2.23 [95% CI 1.25-3.96], p=0.006), as independent predictors of VT recurrence. CONCLUSION: Non-ischemic cardiomyopathy patients were at increased risk of VT recurrence after ablation, although long-term mortality did not differ.

Assessment of the Implementation of Pakistan's National Action Plan on Antimicrobial Resistance in the Agriculture and Food Sectors.

The agriculture and food (agrifood) sectors play key roles in the emergence, spread, and containment of antimicrobial resistance (AMR). Pakistan's first National Action Plan (NAP) on AMR was developed to guide One Health interventions to combat AMR through 2017-2022. To improve subsequent iterations, we assessed the implementation of Pakistan's NAP in the agrifood sectors (NAPag) in October 2022, using the Progressive Management Pathway on AMR tool developed by the Food and Agriculture Organization of the United Nations (FAO). The assessment tool addressed four crucial focus areas of the NAPag: governance, awareness, evidence, and practices. Each focus area contains multiple topics, which involve four sequential stages of activities to progressively achieve systematic management of AMR risk in the agrifood sectors. High-level representatives of the NAPag stakeholders provided information for the assessment through pre-event documentary review and workshop discussions. The assessment results showed that Pakistan's NAPag had an overall moderate coverage (59%) of the anticipated activities. Gaps were particularly notable in strengthening governance, good practices, and interventions in non-livestock sectors. Furthermore, only 12% of the evaluated activities were fully executed and documented, consistently remaining at the planning and piloting stages in the livestock sector across all the examined topics. Insufficient attention to non-livestock sectors, inadequate regulation and enforcement capacity, and resource constraints have hindered scalable and sustainable interventions under the current plan. This assessment provides valuable insights to strengthen the inclusiveness and contribution of the agrifood sectors in the next NAP iteration. In the short-to-medium term, strategic prioritization is necessary to optimize the use of limited resources and target the most critical gaps, such as improving awareness among key stakeholders and fortifying regulations for prudent antimicrobial use. In the long term, integration of AMR into the country's broader health, development, and agricultural transformation agendas will be needed to generate sustainable benefits.

Mechanobiology of the nucleus during the G2-M transition.

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

A Targeted and an Untargeted Metabolomics Approach to Study the Phytochemicals of Tomato Cultivars Grown Under Different Salinity Conditions.

In this study, we evaluated the effect of increasing the salinity of irrigation water on the metabolic content and profiles of two tomato cultivars ('Jaune Flamme' (JF) and 'Red Pear' (RP)) using targeted and untargeted metabolomics approaches. Irrigation of tomato plants was performed with four different salt concentrations provided by chloride (treatment 1) and sulfate (treatment 2) salts. Targeted analysis of the methanolic extract resulted in the identification of nine major polyphenols. Among them, chlorogenic acid, rutin, and naringenin were the prominent compounds in both cultivars. In addition, the quantification of 18 free amino acids from both tomato cultivars showed that different salinity treatments significantly enhanced the levels of glutamine, glutamic acid, and γ-aminobutyric acid (GABA). Using the untargeted metabolomic approach, we identified 129 putative metabolites encompassing a diverse array of phytochemicals including polyphenols, organic acids, lipids, sugars, and amino acids. Principal component analysis (PCA) of mass spectral data acquired under positive and negative ionization modes showed a clear separation between the two cultivars. However, only positive ionization showed separation among different salinity treatments. Unsupervised and supervised learning algorithms were applied to mine the generated data and to pinpoint metabolites different from the two cultivars. These findings suggest that different salinity conditions significantly influenced the accumulation of phytochemicals in tomato cultivars. This study will help tomato breeding programs to develop value-added tomato cultivars under varying environmental conditions.

Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis. / Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real.

BACKGROUND: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. OBJECTIVES: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. METHODS: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. RESULTS: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. CONCLUSIONS: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

FUNDAMENTO: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. OBJETIVOS: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. MÉTODOS: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. RESULTADOS: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. CONCLUSÕES: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.