MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.

Real-life intrinsic capacity screening data from the ICOPE-Care program.

The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: 'Low impairment' (most prevalent), 'Cognition+Locomotion+Hearing+Vision', 'All IC impaired' and 'Psychology+Vitality+Vision'. Compared to individuals with 'Low impairment', those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for 'All IC impaired'. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline.

Development of Magnetic Nanosystems with Potential for the Treatment of Inner Ear Pathologies.

Hearing loss (HL) affects more than 5% of the global population, with projections indicating an impact of up to 50% on young individuals in the next years. HL treatments remain limited due to the inner ear's hermeticism. HL often involves inflammatory processes, underscoring the need for enhanced delivery of antiinflammatory agents to the inner ear. Our research focuses on the development of a directed therapy based on magnetic nanoparticles (MNPs). We previously synthesized biocompatible folic acid-coated iron oxide-core nanoparticles (MNPs@FA) as potential carriers for the anti-inflammatory Diclofenac (Dfc). This study aims to incorporate Dfc onto MNPs@FA to facilitate targeted drug delivery to the inner ear. Through optimizing the loading procedure, we achieved optimal loading capacity. Dfc release was studied in the simulated target fluid and the administration vehicle. Complete characterization is also shown. In vitro biocompatibility testing ensured the biosafety of the resulting formulation. Subsequent ex vivo targeting assays on murine cochleae validated the nanosystems' ability to penetrate the round window membrane, one of the main HL therapy barriers. These findings serve as validation before continuing to more complex in vivo studies. Together, the data here presented represent an advancement in addressing unmet medical needs in HL therapy.

Trityl isocyanide as a general reagent for visible light mediated photoredox-catalyzed cyanations.

A photoredox catalytic strategy has been developed to enable the functionalization of a variety of commercially available, structurally different radical precursors by the use of a bench-stable isonitrile as an efficient cyanating reagent. Specifically, a radical-based reaction has provided a mild and convenient procedure for the cyanation of primary, secondary and tertiary radicals derived from widely accessible sp3-hybridized carboxylic acids, alcohols and halides under visible light irradiation. The reaction tolerates a variety of functional groups and it represents a complementary method for the cyanation of structurally different scaffolds that show diverse native functionalities, expanding the scope of previously reported methodologies.

Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.

The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the insulation of regulatory domains, which in turn might help interpreting the pathological consequences of certain structural variants.

Bio-physical pre-treatments in anaerobic digestion of organic fraction of municipal solid waste to optimize biogas production and digestate quality for agricultural use.

This study optimized the anaerobic digestion (AD) of separated collected organic fractions of municipal solid waste (OFMSW) to produce energy and digestate as biofertilizer. Due to OFMSW's partial recalcitrance to degradation, enzymatic (UPP2, MCPS, USC4, USE2, A. niger) and physical (mechanical blending, heating, hydrodynamic cavitation) pre-treatments were tested. Experimental and modeling approaches were used to compare AD performance regarding energy sustainability and digestate quality. Digestate was separated into solid and liquid fractions, and then chemically and physically characterized by investigating the nutrient release mechanisms. Principal Component Analysis was applied, equally weighing energy and digestate productions. Unlike previous studies focusing only on biogas, this study evaluated the effects of pre-treatments on both biogas and digestate production, viewing AD as a biorefinery process for urban waste valorization. Results showed that all pre-treatments were energetically sustainable, but enzymatic pre-treatments yielded digestates richer in nutrients (increase of 80% N, 200% P and 150% K as compared to OFMSW) and with greater organic matter degradation compared to physical pre-treatments. The liquid fraction of digestate from enzymatic pre-treatments had higher nutrient concentrations, while those from physical pre-treatments had more balanced nutrient content, making them more suitable for fertigation.

Histone Acetyl Transferase 1 Is Overexpressed in Poor Prognosis, High-grade Meningeal and Glial Brain Cancers: Immunohistochemical and Aptahistochemical Study.

Primary malignancies of the central nervous system account for 2% of all cancers in adults and almost 15% in children under 15 years of age. The prognosis of brain anaplastic cancers and glioblastomas remains extremely poor, with devastating survival expectative, and new molecular markers and therapeutic targets are essential. Epigenetic changes constitute an extensive field for the development of new diagnostic and therapeutic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker and therapy target for different malignancies. Data repository analysis showed HAT1 mRNA overexpression in gliomas and has been described its alternative splicing in glioblastomas. Using immunohistochemical and aptahistochemical methods, we analyzed the expression of HAT1 in meningiomas, oligodendrogliomas, and astroglial cancers. We observed that HAT1 overexpression is associated with the most aggressive tumor types and the worse prognosis, as well as with a higher probability of early relapse in meningiomas. Its cytosolic localization correlates with tumor progression and prognosis. Aptamers, synthetic oligonucleotides capable to bind and inhibit a wide variety of targets, are considered as promising diagnostic and therapeutic tools. Aptahistochemistry using the aptamer apHAT610 offered superior results in comparison with the antibody used, as a good example of the potential of aptamers as diagnostic tools for histopathology.

Longitudinal associations in dementia family caregivers of ambivalent feelings and disruptive behaviors with C-reactive protein, interleukin-6, and D-dimer.

OBJECTIVE: Caregivers' ambivalent feelings toward the care recipient have been found to be associated with depression and anxiety. There is no research linking caregivers' ambivalent feelings and cardiovascular risk. This study was aimed to analyze longitudinally the effect of ambivalence on caregivers' cardiovascular risk, defined by circulating levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and D-dimer. METHOD: Participants were 121 dementia family caregivers who were assessed three times during a 2-year period. Sociodemographic and health variables, behavioral and psychological symptoms of dementia (BPSD), ambivalent feelings, and C-reactive protein (CRP), IL-6, and D-dimer values were assessed. Mixed linear models were used to analyze the association between variables, including testing whether ambivalent feelings moderated the links between BPSD and biomarkers. RESULTS: Increases over time in D-dimer were associated with increases in ambivalence, older age, female gender, and body mass index (BMI). Increases over time in CRP were associated with increases in BMI, older age, female gender, and the interaction of BPSD with caregivers' ambivalent feelings. The moderation analysis showed that increased BPSD was significantly associated with increased CRP when caregivers experienced high levels of ambivalence (p = .006). In contrast, BPSD were not significantly associated with CRP when caregivers experienced low levels of ambivalence (p = .73). Increases in IL-6 were associated with female gender and BMI. The tested model explained 42.85%, 33.15%, and 5.36% of longitudinal variance in CRP, D-dimer, and IL-6 levels, respectively. CONCLUSION: The findings suggest that high ambivalent feelings are relevant for understanding cardiovascular vulnerability in dementia caregivers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Malnutrition in Amyotrophic Lateral Sclerosis: Insights from Morphofunctional Assessment and Global Leadership Initiative on Malnutrition Criteria.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease frequently accompanied by malnutrition due to weight loss, increased energy expenditure, and muscle mass loss. This study aimed to evaluate morphofunctional assessment tools as predictors of malnutrition and to investigate their relationship with muscle status and disease severity in ALS patients. A cross-sectional study was conducted with 45 ALS patients at the San Cecilio University Hospital in Granada. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Morphofunctional assessment was performed using Bioimpedance Vectorial Analysis (BIVA), handgrip strength (HGS), and Short Physical Performance Battery (SPPB). Malnutrition prevalence was 38% according to GLIM criteria. Significant differences were observed between malnourished and non-malnourished groups in age (70 ± 9 vs. 62 ± 10 years, p = 0.01), sex (female prevalence: 58.8% vs. 25.0%, p = 0.02), dysphagia prevalence (83% vs. 29%, p < 0.001), PEG/PRG use (35.3% vs. 3.6%, p = 0.01), and ALSFRS-R scores (30 ± 12 vs. 34 ± 12, p = 0.02). Malnourished patients had lower values in anthropometric measurements, muscle mass obtained by BIVA, and phase angle (PA) (4.05 ± 0.8° vs. 5.09 ± 0.8°, p < 0.001). No significant differences were found in muscle strength or functional status. PA showed significant correlations with muscle strength (r = 0.52, p < 0.001) and muscle mass measures (r = 0.48, p < 0.001). Moreover, PA was associated with poorer disease progression and physical performance. In our sample, BIVA metrics such as PA (<4.3°), SPA (<-0.8), body cell mass (<9.2 kg/m), and extracellular water (>49.75%) were identified as malnutrition risk factors. The study underscores the critical importance of comprehensive morphofunctional assessment and the use of advanced diagnostic criteria, for early identification and intervention in malnutrition among people with ALS. Further research is warranted to validate these findings and develop targeted nutritional strategies into routine clinical practice.

Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature.

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks.

Evaluation of the impact of an online video game as an educational intervention on sexual health and the prevention, diagnosis, and treatment of sexually transmitted infection: A randomized controlled trial protocol.

BACKGROUND: The incidence of sexually transmitted infections (STIs) is increasing, especially among young people. Tools are needed to increase knowledge about sex education and STI prevention and treatment. Gamification can be a good training tool for both young people and health professionals. The primary objective of this study is to assess the impact of a training intervention on STI prevention, detection, and treatment in primary care professionals. METHODS/DESIGN: Multicentre cluster randomized controlled trial. Groups of primary care professionals will receive an intervention (online video game on sex education and STIs [SEXIT]) and will be compared with control groups that will not receive the intervention. Group assignments will be randomized by clusters. The study will consist of a pre-post evaluation of the intervention: a knowledge test will be administered before and after the intervention and 3 months after the intervention. This test will also be carried out on the same time sequence in the control groups. The impact of the training intervention will be assessed over a 6-month period, focusing on various variables associated with the clinical management of STIs. This evaluation entails the clinical records of diagnostic tests and antibiotic prescriptions related to the clinical approach to STIs. The required sample size is 262 (131 per group). DISCUSSION: Compared with those in the control group, improvements in knowledge and clinical behavioural outcomes after the intervention are expected for participants in the intervention groups. We plan to develop an educational video game to increase the knowledge about sexuality, STIs and violence. Protocol registered at ISRCTN with reference number ISRCTN17783607.

Review of Advancements in Managing Cardiogenic Shock: From Emergency Care Protocols to Long-Term Therapeutic Strategies.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome of end-organ hypoperfusion that could be associated with multisystem organ failure, presenting a diverse range of causes and symptoms. Despite improving survival in recent years due to new advancements, CS still carries a high risk of severe morbidity and mortality. Recent research has focused on improving early detection and understanding of CS through standardized team approaches, detailed hemodynamic assessment, and selective use of temporary mechanical circulatory support devices, leading to better patient outcomes. This review examines CS pathophysiology, emerging classifications, current drug and device therapies, standardized team management strategies, and regionalized care systems aimed at optimizing shock outcomes. Furthermore, we identify gaps in knowledge and outline future research needs.

Navigating Perceived Stress: Experiences of Nursing Students Completing Internships during the COVID-19 Pandemic in Spain.

Background: University students often experience psychological strains such as academic stress, particularly as they approach the transition into the workforce. This stress may have been heightened for nursing students who completed internships during the COVID-19 pandemic. This study aims to analyze the impact of the COVID-19 pandemic on the perceived stress levels of undergraduate nursing students. Methodology: A cross-sectional descriptive observational study was conducted using the Spanish version of the PSS-10 scale, a validated reduction of the English version PSS-14, to evaluate perceived stress. The responses are Likert-type with a total score range of 0 to 40. Questionnaires were distributed electronically to nursing students across all academic years who were engaged in clinical practice. Participation was voluntary. Results: The study included 487 students, the majority of whom were women (78.4%) with an average age of 23.51 years. Most participants were in their third and fourth years (67%). The mean perceived stress score was 20.65 (SD = 5.62) out of a possible 40, indicating moderate stress levels. Statistically significant differences in perceived stress were found between genders, with women reporting higher stress levels than men (Mann-Whitney U = 15,380.000; p < 0.001). Additionally, a significant correlation was observed between the overall perceived stress score and gender, as well as between specific items on the PSS-10 scale and gender, highlighting the importance of gender-specific stress management interventions. Conclusions: Nursing students reported moderate levels of perceived stress, with women experiencing higher stress levels than men. These findings highlight the need for targeted stress management interventions for nursing students, especially during health crises. Addressing gender-specific stressors and fostering a supportive educational environment will enhance students' well-being, academic success, and professional preparedness.

A systematic review of the socioeconomic impact of mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Mechanical Thrombectomy (MT) is an efficacious treatment for severe acute ischemic stroke patients. However, access to MT is limited in many parts of the world, partly due to economic barriers. The purpose of this systematic review is to provide an updated frame about the socioeconomic impact of MT. METHODS: To carry out this systematic review we used the PRISMA guidelines. We included scientific articles analyzing the socioeconomic impact of MT for acute ischemic stroke, in which MT was compared to best medical therapy (BMT). The online databases of Pubmed, Scopus and Web of Science were used as main sources of information. To carry out the comparative analysis, the incremental cost-effectiveness ratio (ICER) was used, relating the cost to quality-adjusted life-year (QALY). Risk of bias was assessed with the Consensus Health Economic Criteria (CHEC) and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: Eight hundred thirty-two studies were identified in this systematic review. As a result, studies that used cost-effectiveness analysis show that MT saves costs in the long term and cost-utility analysis show that the cost per QALY is reasonable with a mean ICER value of $14242.36/QALY. CONCLUSIONS: MT has a favorable socioeconomic impact, as derived from cost-effectiveness and cost-utility analyses. Therefore, public policies should encourage the implementation of MT for stroke patients around the world.

Functional implications of glycans and their curation: insights from the workshop held at the 16th Annual International Biocuration Conference in Padua, Italy.

Dynamic changes in protein glycosylation impact human health and disease progression. However, current resources that capture disease and phenotype information focus primarily on the macromolecules within the central dogma of molecular biology (DNA, RNA, proteins). To gain a better understanding of organisms, there is a need to capture the functional impact of glycans and glycosylation on biological processes. A workshop titled "Functional impact of glycans and their curation" was held in conjunction with the 16th Annual International Biocuration Conference to discuss ongoing worldwide activities related to glycan function curation. This workshop brought together subject matter experts, tool developers, and biocurators from over 20 projects and bioinformatics resources. Participants discussed four key topics for each of their resources: (i) how they curate glycan function-related data from publications and other sources, (ii) what type of data they would like to acquire, (iii) what data they currently have, and (iv) what standards they use. Their answers contributed input that provided a comprehensive overview of state-of-the-art glycan function curation and annotations. This report summarizes the outcome of discussions, including potential solutions and areas where curators, data wranglers, and text mining experts can collaborate to address current gaps in glycan and glycosylation annotations, leveraging each other's work to improve their respective resources and encourage impactful data sharing among resources. Database URL: https://wiki.glygen.org/Glycan_Function_Workshop_2023.

Circadian Transcriptome Oscillations In Human Adipose Tissue Depend On Napping Status And Link To Metabolic And Inflammatory Pathways.

STUDY OBJECTIVES: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity. METHODS: In this cross-sectional study, we extracted the RNA repeatedly across 24h from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using 6 consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers). RESULTS: With napping, there was a loss of rhythmicity in 88% of genes that showed circadian rhythmicity among non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes up-regulated in nappers. The top up-regulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation. CONCLUSION: These new findings may have implications for our understanding of napping's effects on obesity and metabolic disorders.

Relationship of body composition with middle cerebral artery hemodynamic using compositional data analysis: Toledo Study for Healthy Ageing in middle age.

Excess adipose tissue may promote chronic systemic inflammation and oxidative stress, causing endothelial damage. Early evidence indicates that obesity may be associated with poorer cerebral perfusion. The purpose of this study was to examine the relationship between body composition and cerebral hemodynamics. A total of 248 middle-aged adults (50-58 years old; 55% women) underwent a ramp test on a cycle-ergometer until volitional exhaustion. Gas exchange was assessed on a breath-by-breath basis. Mean middle cerebral artery velocity (MCAv) was measured using transcranial Doppler, and pulsatility index (PI) calculated. Body composition was assessed by dual X-ray absorptiometry. Statistical analyses were performed using a compositional data approach including a three-compartment model for body composition (trunk fat mass, extremities fat mass, and fat-free mass). The unadjusted models for the whole sample showed that trunk fat mass relative to other compartments was negatively associated with MCAvrest, MCAvmax, and gain, and positively associated with PImax; extremities fat mass relative to other compartments was positively associated with MCAvrest and MCAvmax, and negatively associated with PImax; and fat-free mass relative to other compartments was positively associated with PImax. These associations were sex-dependent, remaining in the women's subgroup. However, after adjusting for confounders, these associations became non-significant, except for PImax in the whole sample and women's subgroup. These findings suggest a possible association between cerebral hemodynamics and body composition in middle-aged adults, highlighting sex-specific differences. Moreover, our results indicate that higher trunk fat mass relative to other compartments may negatively impact cerebral hemodynamics, reducing MCAv and increasing PImax.

Responses of fine particulate matter (PM2.5) air quality to future climate, land use, and emission changes: Insights from modeling across shared socioeconomic pathways.

Air pollution induced by fine particulate matter with diameter ≤ 2.5 µm (PM2.5) poses a significant challenge for global air quality management. Understanding how factors such as climate change, land use and land cover change (LULCC), and changing emissions interact to impact PM2.5 remains limited. To address this gap, we employed the Community Earth System Model and examined both the individual and combined effects of these factors on global surface PM2.5 in 2010 and projected scenarios for 2050 under different Shared Socioeconomic Pathways (SSPs). Our results reveal biomass-burning and anthropogenic emissions as the primary drivers of surface PM2.5 across all SSPs. Less polluted regions like the US and Europe are expected to experience substantial PM2.5 reduction in all future scenarios, reaching up to ~5 µg m-3 (70 %) in SSP1. However, heavily polluted regions like India and China may experience varied outcomes, with a potential decrease in SSP1 and increase under SSP3. Eastern China witness ~20 % rise in PM2.5 under SSP3, while northern India may experience ~70 % increase under same scenario. Depending on the region, climate change alone is expected to change PM2.5 up to ±5 µg m-3, while the influence of LULCC appears even weaker. The modest changes in PM2.5 attributable to LULCC and climate change are associated with aerosol chemistry and meteorological effects, including biogenic volatile organic compound emissions, SO2 oxidation, and NH4NO3 formation. Despite their comparatively minor role, LULCC and climate change can still significantly shape future air quality in specific regions, potentially counteracting the benefits of emission control initiatives. This study underscores the pivotal role of changes in anthropogenic emissions in shaping future PM2.5 across all SSP scenarios. Thus, addressing all contributing factors, with a primary focus on reducing anthropogenic emissions, is crucial for achieving sustainable reduction in surface PM2.5 levels and meeting sustainable pollution mitigation goals.

Ex vivo C5b-9 Deposition Test to Monitor Complement Activity in Clinical and Subclinical Atypical Hemolytic Uremic Syndrome and in Transplantation-Associated Thrombotic Microangiopathy.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a complement system (CS)-mediated ultrarare disease that manifests as thrombotic microangiopathy (TMA) with preferential small kidney vessels involvement. Transient CS activation is also observed in secondary TMA or in patients at risk of developing aHUS. There is no gold standard test to monitor disease activity; however, the ex vivo C5b-9 deposition test seems to be a good approach. Methods: We assessed the C5b-9 deposition induced by serum samples of patients with aHUS (n = 8) and with TMA associated with kidney (n = 2), lung (n = 1) or hematopoietic stem cell (HSC) transplantation (HSCT, n = 2) during the acute phase of the disease or in remission. As control for transplant-associated TMA (TA-TMA), we analyzed samples of clinically stable kidney and HSC-transplanted patients without signs of TMA. In addition, we studied 1 child with genetic risk of aHUS during an acute infection. Results: In the acute disease phase or in patients with disease activity despite C5 blockade, a significant increase of C5b-9 deposition was detected. In all patients with clinical response to C5 blockade but one, levels of C5b-9 deposition were within the normal range. Finally, we detected increased C5b-9 deposition levels in an asymptomatic child with genetic risk of aHUS when a concomitant otitis episode was ongoing. Conclusion: The ex vivo C5b-9 deposition test is an auspicious tool to monitor CS activity in aHUS and TA-TMA. In addition, we demonstrate that the test may be useful to detect subclinical increase of CS activity, which expands the spectrum of patients that would benefit from a better CS activity assessment.