Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

PFAS Contamination in Europe: Generating Knowledge and Mapping Known and Likely Contamination with "Expert-Reviewed" Journalism.

While the extent of environmental contamination by per- and polyfluoroalkyl substances (PFAS) has mobilized considerable efforts around the globe in recent years, publicly available data on PFAS in Europe were very limited. In an unprecedented experiment of "expert-reviewed journalism" involving 29 journalists and seven scientific advisers, a cross-border collaborative project, the "Forever Pollution Project" (FPP), drew on both scientific methods and investigative journalism techniques such as open-source intelligence (OSINT) and freedom of information (FOI) requests to map contamination across Europe, making public data that previously had existed as "unseen science". The FPP identified 22,934 known contamination sites, including 20 PFAS manufacturing facilities, and 21,426 "presumptive contamination sites", including 13,745 sites presumably contaminated with fluorinated aqueous film-forming foam (AFFF) discharge, 2911 industrial facilities, and 4752 sites related to PFAS-containing waste. Additionally, the FPP identified 231 "known PFAS users", a new category for sites with an intermediate level of evidence of PFAS use and considered likely to be contamination sources. However, the true extent of contamination in Europe remains significantly underestimated due to a lack of comprehensive geolocation, sampling, and publicly available data. This model of knowledge production and dissemination offers lessons for researchers, policymakers, and journalists about cross-field collaborations and data transparency.

Implementation of a PCR-based strategy to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU). METHODS: We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy. RESULTS: Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control. CONCLUSIONS: The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU.

High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase.

Ceramide has a key role in the regulation of cellular senescence and apoptosis. As Ceramide levels are lowered by the action of acid ceramidase (AC), abnormally expressed in various cancers, the identification of AC inhibitors has attracted increasing interest. However, this finding has been mainly hampered by the lack of formats suitable for the screening of large libraries. We have overcome this drawback by adapting a fluorogenic assay to a 384-well plate format. The performance of this optimised platform has been proven by the screening a library of 4100 compounds. Our results show that the miniaturised platform is well suited for screening purposes and it led to the identification of several hits, that belong to different chemical classes and display potency ranges of 2-25 µM. The inhibitors also show selectivity over neutral ceramidase and retain activity in cells and can therefore serve as a basis for further chemical optimisation.

The Montecristo mining district, northern Chile: the relationship between vein-like magnetite-(apatite) and iron oxide-copper-gold deposits.

The Montecristo district, northern Chile, is one of the few places worldwide where there is a direct relationship between magnetite-(apatite) (MtAp) mineralization and iron oxide-copper-gold (IOCG) mineralization. The MtAp mineralization includes Ti-poor magnetite, fluorapatite, and actinolite and is crosscut and partially replaced by a younger IOCG mineralization that includes a second generation of actinolite and magnetite with quartz, chalcopyrite, pyrite, and molybdenite. The MtAp stage at Montecristo is interpreted as the crystallized iron-rich melts that used the pre-existing structures of the Atacama Fault System as conduits. These rocks later acted as a trap for hydrothermal IOCG mineralization. Geochronology data at Montecristo indicate that the host diorite (U-Pb zircon 153.3 ± 1.8 Ma, 2-sigma), MtAp mineralization (40Ar-39Ar in actinolite, 154 ± 2 Ma and 153 ± 4 Ma, 2-sigma), and the IOCG event (Re-Os on molybdenite, 151.8 ± 0.6 Ma, 2-sigma) are coeval within error and took place in a time span of less than 3.4 Ma. The εHfi and εNdi values of the host diorite are + 8.0 to + 9.8 and + 4.3 to + 5.4, respectively. The whole-rock 87Sr/86Sri values of the IOCG mineralization (0.70425 to 0.70442) are in the lower end of those of the MtAp mineralization (0.70426-0.70629). In contrast, εNdi values for the IOCG mineralization (+ 5.4 and + 5.7) fall between those of the MtAp rocks (+ 6.6 to + 7.2) and the host diorite, which suggests that the IOCG event was related to fluids having a more crustal Nd (εNdi < + 5.7) composition than the MtAp mineralization. This likely reflects the mixing of Nd from the MtAp protolith and a deep magmatic-hydrothermal source, very likely an unexposed intrusion equivalent to the host diorite. Sulfur isotope compositions (δ34S, + 0.3 to + 3.4‰) are consistent with a magmatic source. Supplementary Information: The online version contains supplementary material available at 10.1007/s00126-023-01172-0.

Community assembly and metaphylogeography of soil biodiversity: Insights from haplotype-level community DNA metabarcoding within an oceanic island.

Most of our understanding of island diversity comes from the study of aboveground systems, while the patterns and processes of diversification and community assembly for belowground biotas remain poorly understood. Here, we take advantage of a relatively young and dynamic oceanic island to advance our understanding of ecoevolutionary processes driving community assembly within soil mesofauna. Using whole organism community DNA (wocDNA) metabarcoding and the recently developed metaMATE pipeline, we have generated spatially explicit and reliable haplotype-level DNA sequence data for soil mesofaunal assemblages sampled across the four main habitats within the island of Tenerife. Community ecological and metaphylogeographic analyses have been performed at multiple levels of genetic similarity, from haplotypes to species and supraspecific groupings. Broadly consistent patterns of local-scale species richness across different insular habitats have been found, whereas local insular richness is lower than in continental settings. Our results reveal an important role for niche conservatism as a driver of insular community assembly of soil mesofauna, with only limited evidence for habitat shifts promoting diversification. Furthermore, support is found for a fundamental role of habitat in the assembly of soil mesofauna, where habitat specialism is mainly due to colonization and the establishment of preadapted species. Hierarchical patterns of distance decay at the community level and metaphylogeographical analyses support a pattern of geographic structuring over limited spatial scales, from the level of haplotypes through to species and lineages, as expected for taxa with strong dispersal limitations. Our results demonstrate the potential for wocDNA metabarcoding to advance our understanding of biodiversity.

The Covid-19 pandemic reinforces the need for sustainable health planning.

The 2030 Agenda for Sustainable Development highlighted the growing attention to the adequacy of health planning models to sustainable development. A re-reading of the results of a round table debate on "sustainable planning", which took place at the 5th National Congress of Tropical Medicine (Portugal, 2019) under a participant observation strategy, framed by the findings of a "synthesis of better evidence" literature review and cross-referenced with the reflections of different authors and experts about the momentum created by the COVID-19 pandemic, underlined the challenges to sustainable health planning that have emerged and are projected beyond the current pandemic context. Variable perceptions of the term "sustainable health development", leading to the potential loss of their relevance in guiding the elaboration of policies and strategic plans, and the potential higher effectiveness of the participatory approaches of health planning in achieving sustainable health were highlighted in the debate and literature, in general and in public health emergency contexts. Those results gained new relevance during the current COVID-19 pandemic, bringing back to the forefront a reflection of the inadequate planning framework that has usually been used to understand and respond to global health challenges, despite the already existing experience, evidence and support instruments.

Methuosis Contributes to Jaspine-B-Induced Cell Death.

Methuosis is a type of programmed cell death in which the cytoplasm is occupied by fluid-filled vacuoles that originate from macropinosomes (cytoplasmic vacuolation). A few molecules have been reported to behave as methuosis inducers in cancer cell lines. Jaspine B (JB) is a natural anhydrous sphingolipid (SL) derivative reported to induce cytoplasmic vacuolation and cytotoxicity in several cancer cell lines. Here, we have investigated the mechanism and signalling pathways involved in the cytotoxicity induced by the natural sphingolipid Jaspine B (JB) in lung adenocarcinoma A549 cells, which harbor the G12S K-Ras mutant. The effect of JB on inducing cytoplasmic vacuolation and modifying cell viability was determined in A549 cells, as well as in mouse embryonic fibroblasts (MEF) lacking either the autophagy-related gene ATG5 or BAX/BAK genes. Apoptosis was analyzed by flow cytometry after annexin V/propidium iodide staining, in the presence and absence of z-VAD. Autophagy was monitored by LC3-II/GFP-LC3-II analysis, and autophagic flux experiments using protease inhibitors. Phase contrast, confocal, and transmission electron microscopy were used to monitor cytoplasmic vacuolation and the uptake of Lucifer yellow to assess macropinocyosis. We present evidence that cytoplasmic vacuolation and methuosis are involved in Jaspine B cytotoxicity over A549 cells and that activation of 5' AMP-activated protein kinase (AMPK) could be involved in Jaspine-B-induced vacuolation, independently of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 1 (PI3K/Akt/mTORC1) axis.

Flightlessness in insects enhances diversification and determines assemblage structure across whole communities.

Dispersal limitation has been recurrently suggested to shape both macroecological patterns and microevolutionary processes within invertebrates. However, because of potential interactions among biological, environmental, temporal, and spatial variables, causal links among flight-related traits, diversification and spatial patterns of community assembly remain elusive. Integrating genetic variation within species across whole insect assemblages, within a simplified spatial and environmental framework, can be used to reduce the impact of these potentially confounding variables. Here, we used standardized sampling and mitochondrial DNA sequencing for a whole-community characterization of the beetle fauna inhabiting a singular forested habitat (laurel forest) within an oceanic archipelago setting (Canary Islands). The spatial structure of species assemblages together with species-level genetic diversity was compared at the archipelago and island scales for 104 winged and 110 wingless beetle lineages. We found that wingless beetle lineages have: (i) smaller range sizes at the archipelago scale, (ii) lower representation in younger island communities, (iii) stronger population genetic structure, and (iv) greater spatial structuring of species assemblages between and within islands. Our results reveal that dispersal limitation is a fundamental trait driving diversity patterns at multiple hierarchical levels by promoting spatial diversification and affecting the spatial configuration of entire assemblages at both island and archipelago scales.

Synthesis and characterization of bichromophoric 1-deoxyceramides as FRET probes.

The suitability as FRET probes of two bichromophoric 1-deoxydihydroceramides containing a labelled spisulosine derivative as a sphingoid base and two differently ω-labelled fluorescent palmitic acids has been evaluated. The ceramide synthase (CerS) catalyzed metabolic incorporation of ω-azido palmitic acid into the above labeled spisulosine to render the corresponding ω-azido 1-deoxyceramide has been studied in several cell lines. In addition, the strain-promoted click reaction between this ω-azido 1-deoxyceramide and suitable fluorophores has been optimized to render the target bichromophoric 1-deoxydihydroceramides. These results pave the way for the development of FRET-based assays as a new tool to study sphingolipid metabolism.

Vestibular rehabilitation with mobile posturography as a "low-cost" alternative to vestibular rehabilitation with computerized dynamic posturography, in old people with imbalance: a randomized clinical trial.

BACKGROUND: Vestibular rehabilitation (VR), specifically, VR with dynamic computerized posturography (CDP) has proven to be useful to improve balance and reduce the risk of falling in old patients. Its major handicap is probably its cost, which has hindered its generalisation. One solution to reduce this cost is performing VR with mobile posturography systems, which allow assessment of stability at the center of body mass in daily-life conditions. Also, rehabilitation with vibrotactile neurofeedback training could be used in dynamic tasks. OBJECTIVE: To assess whether two different protocols of vestibular rehabilitation (using CDP and the Vertiguard system) show significant differences in the improvement of balance among older persons with imbalance METHODS: A clinical trial comparing VR with CDP exercises and VR with mobile posturography (Vertiguard) exercises, was designed. The participants were people over 65 years, with imbalance. The composite (average balance) in the sensory organization test (SOT) of the CDP was the main outcome measure; it was compared before and 3 weeks after VR, and between both intervention groups. RESULTS: 40 patients were included in the study (19 in the CDP-VR group and 21 in the Vertiguard-VR group). Average balance was significantly improved in both intervention groups (51% pre-VR vs 60% post-VR, p = 0.002, CDP-VR group; 49% pre-VR vs 57% post-VR, p = 0.008, Vertiguard-VR group); no significant differences in this improvement were found comparing both groups (p = 0.580). DISCUSSION AND CONCLUSIONS: VR using mobile posturography is useful to improve stability in old people with instability, showing similar improvement rates to those of VR using CDP. UNIQUE IDENTIFIER: NCT03034655 www.clinicaltrials.gov Registered on 25 January 2017.

A new approach for calculating microalgae culture growth based on an inhibitory effect of the surrounding biomass.

Ever since the potential of algae in biotechnology was recognized, models describing the growth of algae inside photobioreactors have been proposed. These models are the basis for the optimization of process conditions and reactor designs. Over the last few decades, models became more and more elaborate with the increase of computational capacity. Thus far, these models have been based on light attenuation due to the absorption and scattering effects of the biomass. This manuscript presents a new way of predicting the apparent growth inside photobioreactors using simple models for enzymatic kinetics to describe the reaction between photons and the photosynthetic unit. The proposed model utilizes an inhibition kinetic formula based on the surrounding biomass to describe the average growth rate of a culture, which is determined by the local light intensities inside the reactor. The result is a mixed-inhibition scheme with multiple inhibition sites. The parameters of the new kinetic equation are replaced by empirical regression functions to correlate their dependency on incident light intensity and reactor size. The calibrations of the parameters and the regression functions are based on the numerical solutions of the growth rate computed with a classical Type II model. As a final verification, we apply the new equation in predicting the growth behavior of three phototrophic organisms in reactors of three different sizes.

Scoping review of trials evaluating adhesive strategies in pediatric dentistry: where do simplified strategies lie?

BACKGROUND: Adhesive restorations allow a conservative approach to caries management and are increasingly used as a restorative option in pediatric dentistry. Placement can be difficult in children because of the cooperation required for multiple bonding steps. Due to this, it is vital to assess if novel, simpler strategies have been featured in clinical trials and if clinical trials are researching the different existing adhesive strategies. METHODS: This review followed Preferred Reporting Items for Systematic Reviews and Meta-analysis adapted for Scoping Reviews (PRISMA-ScR) guidelines. PubMed/Medline, Cochrane Central, Scopus and EMBASE were used for systematic search, using free keywords and controlled search terms. Clinical trials of children requiring a restorative intervention which featured adhesive strategies were included. Only peer-reviewed trials of primary teeth restored with resin composites, published in the last 10-year period were eligible. Data charting was accomplished independently by two reviewers, and studies were summarized according to their date, type, intervention, sample size, observation period, outcomes and conclusions. Quality assessment was performed using Cochrane's Risk of Bias 2.0 tool. RESULTS: 700 potentially relevant references were found, which after a rigorous inclusion scheme, resulted in a total of 8 eligible clinical trials. Out of these, 7 were randomized clinical trials. Most trials featured a split-mouth design and the observation period ranged from 12 to 36 months. The trials evaluated interventions of two self-adhesive composites, two bulk-fill composites, two novel composites, one compomer and eight adhesives from different strategies. Most studies (4/8) included were judged to raise some concerns regarding risk of bias, while two were classified as high risk and two as low. CONCLUSION: Few studies comparing adhesive strategies were found, especially adhesives in sound substrates. The existing studies do not reflect all current approaches that could be used in pediatric dentistry. Further studies addressing bioactive composites and contemporary adhesives are necessary.

Climate drives community-wide divergence within species over a limited spatial scale: evidence from an oceanic island.

Geographic isolation substantially contributes to species endemism on oceanic islands when speciation involves the colonisation of a new island. However, less is understood about the drivers of speciation within islands. What is lacking is a general understanding of the geographic scale of gene flow limitation within islands, and thus the spatial scale and drivers of geographical speciation within insular contexts. Using a community of beetle species, we show that when dispersal ability and climate tolerance are restricted, microclimatic variation over distances of only a few kilometres can maintain strong geographic isolation extending back several millions of years. Further to this, we demonstrate congruent diversification with gene flow across species, mediated by Quaternary climate oscillations that have facilitated a dynamic of isolation and secondary contact. The unprecedented scale of parallel species responses to a common environmental driver for evolutionary change has profound consequences for understanding past and future species responses to climate variation.

A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor.

The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.

Does patient environment have any influence on balance?

BACKGROUND: Although patient environment is a factor to consider when planning a vestibular rehabilitation program, there are no studies correlating this factor to outcomes of balance assessment. AIM: To evaluate whether there are differences in objective evaluation of balance in elderly patients at risk of falls according to the environment in which they live (urban or rural) and their lifestyle (considering cardiovascular risk factors). METHODS: Cross-sectional study of a sample of 139 elderly patients with high risk of falls assessed with objective outcome measures: Computer Dynamic Posturography (CDP), and the modified Timed Up-and-Go (TUG) test; and subjective outcome measures: Dizziness Handicap Inventory (DHI) and short Falls Efficacy Scale-International (short FES-I). Rural or urban environment was defined according to administrative and legal criteria. RESULTS: Elderly patients at risk of fall living in rural environment show better composite results in SOT with better scores in Condition 6 and fewer falls during the CDP. They also require fewer steps to perform the TUG test. DISCUSSION: The present study provides evidence that patient environment has an influence in balance. CONCLUSION: Patient environment should be considered when analyze tests evaluating static and dynamic balance.

Prognostic factors that modify outcomes of vestibular rehabilitation in elderly patients with falls.

BACKGROUND: Our previous study has shown that vestibular rehabilitation (VR) is an effective technique to reduce falls in elderly patients. It would be interesting to establish patients' clinical characteristics in which vestibular rehabilitation is expected to be more effective. AIMS: Evaluate factors that could modify rehabilitation outcomes in elderly patients with previous falls. METHODS: Fifty-seven patients randomized to one of the intervention group (computerized dynamic posturography-CDP-training, optokinetic stimulus or exercise at home) and with previous falls were analyzed. Patients were assessed with objective outcome measures (sensorial organization test and limits of stability-LOS-of CDP, modified timed up and go test-TUG-and number of falls) and with subjective outcome measures (dizziness handicap inventory and Short falls efficacy scale-international-Short FES-I) during a 12-month follow-up period. RESULTS: In the logistic regression model, a worse score in the maximum excursion (MXM), and a shorter time in the TUG significantly associated with a reduction > 50% of falls. Also, association with a higher score in the Short FES-I was close to a statistical significance. There was no statistical significance association with other covariables. DISCUSSION: In patients with reduced limits of stability, VR seems to be more effective and they should be encouraged to perform it. But on the other hand, patients with longer time in the TUG show worse outcomes and may benefit more with gait training. CONCLUSIONS: VR in elderly people with previous falls is effective regardless of their age and gender.

A Distributed Clustering Algorithm Guided by the Base Station to Extend the Lifetime of Wireless Sensor Networks.

Clustering algorithms are necessary in Wireless Sensor Networks to reduce the energy consumption of the overall nodes. The decision of which nodes are the cluster heads (CHs) greatly affects the network performance. The centralized clustering algorithms rely on a sink or Base Station (BS) to select the CHs. To do so, the BS requires extensive data from the nodes, which sometimes need complex hardware inside each node or a significant number of control messages. Alternatively, the nodes in distributed clustering algorithms decide about which the CHs are by exchanging information among themselves. Both centralized and distributed clustering algorithms usually alternate the nodes playing the role of the CHs to dynamically balance the energy consumption among all the nodes in the network. This paper presents a distributed approach to form the clusters dynamically, but it is occasionally supported by the Base Station. In particular, the Base Station sends three messages during the network lifetime to reconfigure the s k i p value of the network. The s k i p , which stands out as the number of rounds in which the same CHs are kept, is adapted to the network status in this way. At the beginning of each group of rounds, the nodes decide about their convenience to become a CH according to a fuzzy-logic system. As a novelty, the fuzzy controller is as a Tagaki-Sugeno-Kang model and not a Mandami-one as other previous proposals. The clustering algorithm has been tested in a wide set of scenarios, and it has been compared with other representative centralized and distributed fuzzy-logic based algorithms. The simulation results demonstrate that the proposed clustering method is able to extend the network operability.

The Potential of Proteolytic Chimeras as Pharmacological Tools and Therapeutic Agents.

The induction of protein degradation in a highly selective and efficient way by means of druggable molecules is known as targeted protein degradation (TPD). TPD emerged in the literature as a revolutionary idea: a heterobifunctional chimera with the capacity of creating an interaction between a protein of interest (POI) and a E3 ubiquitin ligase will induce a process of events in the POI, including ubiquitination, targeting to the proteasome, proteolysis and functional silencing, acting as a sort of degradative knockdown. With this programmed protein degradation, toxic and disease-causing proteins could be depleted from cells with potentially effective low drug doses. The proof-of-principle validation of this hypothesis in many studies has made the TPD strategy become a new attractive paradigm for the development of therapies for the treatment of multiple unmet diseases. Indeed, since the initial protacs (Proteolysis targeting chimeras) were posited in the 2000s, the TPD field has expanded extraordinarily, developing innovative chemistry and exploiting multiple degradation approaches. In this article, we review the breakthroughs and recent novel concepts in this highly active discipline.

New fluorogenic probes for neutral and alkaline ceramidases.

New fluorogenic ceramidase substrates derived from the N-acyl modification of our previously reported probes (RBM14) are reported. While none of the new probes were superior to the known RBM14C12 as acid ceramidase substrates, the corresponding nervonic acid amide (RBM14C24:1) is an efficient and selective substrate for the recombinant human neutral ceramidase, both in cell lysates and in intact cells. A second generation of substrates, incorporating the natural 2-(N-acylamino)-1,3-diol-4-ene framework (compounds RBM15) is also reported. Among them, the corresponding fatty acyl amides with an unsaturated N-acyl chain can be used as substrates to determine alkaline ceramidase (ACER)1 and ACER2 activities. In particular, compound RBM15C18:1 has emerged as the best fluorogenic probe reported so far to measure ACER1 and ACER2 activities in a 96-well plate format.