A new instrumentation for simultaneous terahertz and mid-infrared spectroscopy in corrosive gaseous mixtures.

The correct interpretation of infrared (IR) observations of planetary atmospheres requires an accurate knowledge of temperature and partial and global pressures. Precise laboratory measurements of absorption intensities and line profiles, in the 200-350 K temperature range, are, therefore, critical. However, for gases only existing in complex chemical equilibria, such as nitrous or hypobromous acids, it is not possible to rely on absolute pressure measurements to measure absolute integrated optical absorption cross sections or IR line intensities. To overcome this difficulty, a novel dual-beam terahertz (THz)/mid-IR experimental setup has been developed, relying on the simultaneous use of two instruments. The setup involves a newly constructed temperature-controlled (200-350 K) cross-shaped absorption cell made of inert materials. The cell is traversed by the mid-IR beam from a high-resolution Fourier transform spectrometer using along a White-cell optical configuration providing absorption path lengths from 2.8 to 42 m and by a THz radiation beam (82.5 GHz to 1.1 THz), probing simultaneously the same gaseous sample. The THz channel records pure rotational lines of molecules for which the dipole moment was previously measured with high precision using Stark spectroscopy. This allows for a determination of the partial pressure in the gaseous mixture and enables absolute line intensities to be retrieved for the mid-IR range. This new instrument opens a new possibility for the retrieval of spectroscopic parameters for unstable molecules of atmospheric interest. The design and performance of the equipment are presented and illustrated by an example of simultaneous THz and mid-IR measurement on nitrous acid (HONO) equilibrium.

Time to intestinal clearance of carbapenemase-producing Enterobacterales in hospital patients: a longitudinal retrospective observational cohort study.

BACKGROUND: Intestinal clearance of carbapenemase-producing Enterobacterales (CPE-IC) is a cornerstone to discontinue isolation precautions for CPE patients in hospitals. This study aimed to evaluate the time to spontaneous CPE-IC and identify its potential associated risk factors. METHODS: This retrospective cohort study was carried out between January 2018 and September 2020 on all patients in a 3200-bed teaching referral hospital with confirmed CPE intestinal carriage. CPE-IC was defined as at least three consecutive CPE-negative rectal swab cultures without a subsequent positive result. A survival analysis was performed to determine the median time to CPE-IC. A multivariate Cox model was implemented to explore the factors associated with CPE-IC. RESULTS: A total of 110 patients were positives for CPE, of whom 27 (24.5%) achieved CPE-IC. Median time to CPE-IC was 698 days. Univariate analysis showed that female sex (P=0.046), multiple CPE-species in index cultures (P=0.005), Escherichia coli or Klebsiella spp. (P=0.001 and P=0.028, respectively) were significantly associated with the time to CPE-IC. Multivariate analysis highlighted that identification of E. coli carbapenemase-producing or CPEs harbouring ESBL genes in index culture extended the median time to CPE-IC, respectively (adjusted hazard ratio (aHR) = 0.13 (95% confidence interval: 0.04-0.45]; P=0.001 and aHR = 0.34 (95% confidence interval: 0.12-0.90); P=0.031). CONCLUSION: Intestinal decolonization of CPE can take several months to years to occur. Carbapenemase-producing E. coli are likely to play a key role in delaying intestinal decolonization, probably through horizontal gene transfer between species. Therefore, discontinuation of isolation precautions in CPE-patients should be considered with caution.

Are there socio-economic inequities in access to reperfusion therapy: The stroke 69 cohort.

BACKGROUND AND PURPOSE: Low socio-economic status of individuals has been reported to be associated with a higher incidence of stroke and influence the diagnosis after revascularization. However, whether it is associated with poorer acute stroke management is less clear. To determine whether social deprivation was associated with a poorer access to reperfusion therapy, either intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) in a population-based cohort. METHODS: Over a 14-month period, all consecutive adult patients admitted to any emergency department or a comprehensive or primary stroke center (CSC/PSC) of the Rhône county with a confirmed ischemic stroke were included. The socioeconomic status of each patient was measured using the European Deprivation Index (EDI). The association between EDI and access to reperfusion therapy was assessed in univariate and multivariate logistic regression analyses. RESULTS: Among the 1226 consecutive IS patients, 316 (25%) were admitted directly in a PSC or CSC, 241 (19.7%) received a reperfusion therapy; 155 IVT alone, 20 EVT alone, and 66 both therapies. Median age was 79 years, 1030 patients had an EDI level of 1 to 4, and 196 an EDI of 5 (the most deprived group). The most deprived patients (EDI level 5) did not have a poorer access to reperfusion therapy compared to all other patients in univariate (OR 1.22, 95%CI [0.85; 1.77]) nor in multivariate analyses (adjOR 0.97, 95%CI [0.57; 1.66]). CONCLUSIONS: We did not find any significant association between socioeconomic deprivation and access to reperfusion therapy. This suggests that the implementation of EVT was not associated with increased access inequities.

Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations.

BACKGROUND: Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of this retrospective study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate. METHOD: We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population (n = 1210) and a selected "top cycle" population (n = 677), after blastocyst transfer on day 5 or cleaved embryo transfer on day 3. The selected couples had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the progesterone to oocyte index (POI), the progesterone:estradiol ratio (P:E2 ratio), and the progesterone to follicle (> 14 mm) index (PFI). RESULTS: In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p <  0.01); the same was true for the birth rate (32.1 and 22.8%, respectively, p <  0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate, and 33.9 and 34.9% for the birth rate). The serum progesterone levels on the eve of the trigger day and on the day itself were significantly lower in the pregnant women (p <  0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other researchers. The POI and the PFI appear to have predictive value for cleaved embryos transfers. CONCLUSIONS: Blastocyst transfers were associated with higher clinical pregnancy and birth rates than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.

Provision of information on transplantation to cystic fibrosis patients and their relatives: Overview of French practices and recommendations.

BACKGROUND: How health-care professionals inform cystic fibrosis patients and their relatives about transplantation is not well known. Such information may not be provided in a timely or satisfactory manner. We conducted a survey about patient information practices among professionals from all French cystic fibrosis centers and transplant centers, to determine how they might be improved. METHODS: This was a national, retrospective, multicenter, descriptive assessment of practices involving health-care professionals, transplant recipients and their relatives, and peer patients who are themselves transplant recipients. Questionnaires were developed by the French working group on cystic fibrosis patient education (GETHEM: Groupe éducation thérapeutique et mucoviscidose). At the end of the questionnaires, respondents were invited to suggest ways to improve the current process. RESULTS: In all, 216 professionals, 55 patients, 30 relatives of these patients, and 17 peer patients responded to the questionnaires, which addressed topics in chronological order, from neonatal screening or later diagnosis of the illness to the time of the transplant, if one was performed. CONCLUSIONS: Study findings have allowed us to draft nine recommendations for professionals to improve patient information practices. A booklet now being prepared aims to facilitate the process for professionals, and e-learning modules are also forthcoming.

Decrease of spermatozoa with an unbalanced chromosome content after cell sorting in men carrying a structural chromosomal abnormality.

BACKGROUND: We showed that in men with a constitutional chromosomal abnormality, DNA fragmentation was significantly higher in chromosomally unbalanced spermatozoa than in spermatozoa with a normal or balanced chromosomal content. These results could be explained by a phenomenon already described in infertile men: abortive apoptosis. OBJECTIVES: To determine whether magnetic-activated cell separation could select spermatozoa with lower levels of DNA fragmentation and unbalanced chromosome content in men carrying a structural chromosomal abnormality. MATERIALS AND METHODS: The spermatozoa of ten males with a chromosomal rearrangement were separated into two populations using magnetic-activated cell separation (annexin V (-) and annexin V (+) fractions), in order to study meiotic segregation by fluorescence in situ hybridization, the percentage of spermatozoa with an externalization of phosphatidylserine by annexin V staining and DNA fragmentation by TdT-mediated dUTP nick-end labeling on the whole ejaculate and on selected spermatozoa in the same patient. RESULTS: For all patients, the percentage of spermatozoa with externalization of phosphatidylserine decreased in the annexin V (-) fraction and increased in the annexin V (+) fraction as compared to the frozen-thawed semen sample. The rates of DNA fragmentation were statistically much lower in the annexin V (-) fraction when compared to the rate before magnetic-activated cell separation for all but one patient. Conversely, we observed a statistically significantly higher rate of DNA fragmentation in the annexin V (+) fraction for six patients. After magnetic-activated cell separation, there was a significant increase of normal/balanced spermatozoa in the fraction of annexin V (-) for all patients. Conversely, we observed a significant decrease in the fraction of annexin V (+) for seven patients. DISCUSSION AND CONCLUSIONS: Magnetic-activated cell separation is a promising tool for increasing the selection of healthy spermatozoa, with a decrease in the number of spermatozoa with externalization of phosphatidylserine, DNA fragmentation, and chromosome unbalance, for use in assisted reproductive technologies such as intracytoplasmic sperm injection for males with a chromosomal structural abnormality.

Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

Design of a rotating disk reactor to assess the colonization of biofilms by free-living amoebae under high shear rates.

The present study was aimed at designing and optimizing a rotating disk reactor simulating high hydrodynamic shear rates (γ), which are representative of cooling circuits. The characteristics of the hydrodynamic conditions in the reactor and the complex approach used to engineer it are described. A 60 l tank was filled with freshwater containing free-living amoebae (FLA) and bacteria. Adhesion of the bacteria and formation of a biofilm on the stainless steel coupons were observed. FLA were able to establish in these biofilms under γ as high as 85,000 s-1. Several physical mechanisms (convection, diffusion, sedimentation) could explain the accumulation of amoeboid cells on surfaces, but further research is required to fully understand and model the fine mechanisms governing such transport under γ similar to those encountered in the industrial environment. This technological advance may enable research into these topics.

Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

The benefit of the systematic revision of the acetabular implant in favor of a dual mobility articulation during the treatment of periprosthetic fractures of the femur: a 49 cases prospective comparative study.

INTRODUCTION: The SOFCOT symposium (2005) on periprosthetic fractures of the femur (PFFs) highlighted a high rate of dislocation (15.6% at 6 months) after change of prosthesis. So far, no study has ever proved the benefit of dual-mobility articulation during PFFs revisions. We conducted a comparative study on two prospective cohorts in order to (1) assess the influence of systematic acetabular revision in favor of a double mobility on dislocation rate (2) and in order to evaluate the rate of morbidity associated with this extra surgical procedure. HYPOTHESIS: A systematic replacement of the cup in favor of a dual-mobility articulation enables to reduce the dislocation rate in PFFs revisions without increasing morbidity. METHODOLOGY: We compared two prospective multicenter cohorts over a year (2005 and 2015) using the same methodology. Any fracture around hip prosthesis which occurred 3 months at least after surgery was included. Data collection was clinical and radiological on preoperative, intraoperative and 6 months after surgery. The 2015 "bipolar" group (n = 24) included patients who had a bipolar revision (both femoral and dual-mobility articulation). The 2005 "unipolar" group (n = 25) included patients who had only a femoral implant revision. Patients were comparable by age (p = 0.36), sex (p = 0.91), ASA score (p = 0.36), history of prosthetic revision (p = 1.00), Katz score (p = 0.50) and the type of fracture according to the Vancouver classification (p = 0.55). RESULTS: There was a 4% rate of dislocation in the "bipolar group" while there was 21% rate of dislocation in the "unipolar group" (8% of recurrent dislocation) (p = 0.19). The rate of all-cause complications 6 months after surgery was not significantly different (p = 0.07): 12.5% in the 2015 "bipolar" cohort (one dislocation, one non-symptomatic cup migration and one pseudarthrosis of the major trochanter) versus 35% in the "unipolar" cohort (5 dislocations, 1 major trochanter fracture and 1 femur pseudarthrosis, 1 secondary displacement associated with a superficial infection). The surgical revision after 6 months was not significantly different (1/23 or 4% vs. 4/25 or 16%, p = 0.35). CONCLUSION: We confirm the low rate of dislocations after fitting a dual-mobility cup in case of revision of the femoral side in case of periprosthetic femoral fracture, as well as the need for additional cases to be carried out upon further studies to significantly confirm the interest of preventing instability after femoral revision.

Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support on a pain test.

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.

The Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries.

BACKGROUND: Hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, potentially fatal, bradykinin-mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults. OBJECTIVE: To compare demographics, disease characteristics and treatment outcomes of icatibant-treated HAE attacks in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the UK. METHODS: The Icatibant Outcome Survey [IOS; Shire, Zug, Switzerland (NCT01034969)] is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009-April 2015. RESULTS: Overall, 481 patients with C1-INH-HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found although no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P = 0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self-administration in all countries. Overall, significant differences (all P < 0.001) were found across countries in time to treatment [median 1.8 h; median range: 0.0 (Germany-Austria) to 4.4 (France) h], time to resolution [median 6.5 h; median range: 3 (Germany-Austria) to 12 (France) h] and attack duration [median 10.5 h; median range: 3.1 (Germany-Austria) to 18.5 (France) h]. CONCLUSION: These data form the first European cross-country comparison of disease characteristics and icatibant use in patients with C1-INH-HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country-specific parameters driving regional variations in icatibant use.

Sperm RNA preparation for transcriptomic analysis: Review of the techniques and personal experience.

In the last 10 years, several approaches, including microarrays, have been applied to investigate sperm transcript levels. However, success using microarray profiling is highly dependent of the quality of the RNA obtained. Therefore, the development of methods that deliver highly purified and intact RNA is of utmost importance. The three steps used to achieve this goal, purification of spermatozoa, RNA extraction and evaluation of RNA quality, are reviewed. Following that review and preliminary experiments, we processed sperm samples from seven normozoospermic men with a combination of gradient centrifugation and somatic cell lysis. RNA was extracted using the NucleoSpin RNA XS kit (Macherey-Nagel) and its purity checked using the BioAnalyzer. Hybridisation was done on Agilent SurePrint G3 Human GE 8 × 60K V2 microarrays. We identified 900 transcripts among the 1000 high abundance sperm transcripts reported in the literature. These genes are known to be involved in several biological processes, notably spermatogenesis, transcription regulation, cell growth and differentiation, sperm motility and capacitation, fertilisation, and embryogenesis. Therefore, our methodology is highly suitable for sperm transcriptomic analyses and can be used, notably, to compare mRNA profiles between fertile and infertile males.

Reproducibility of single-pass donor DSAEK tissue preparation with the MORIA single-use microkeratome.

PURPOSE: To assess the reproducibility of single-pass cutting for preparation of ultra-thin (≤120µm) donor cornea grafts in Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: All consecutive patients of DSAEK performed using the MORIA One Use microkeratome (MORIA, Antony, France) in between June 2014 and August 2015. Patient and donor central corneal thickness (CTT), microkeratome head, remaining stromal bed thickness (RSBT), number of cut and graft thickness at 1 month and 6 months postoperatively were recorded in this single-center prospective study. RESULTS: The mean preoperative donor graft CCT was 569.0±45.1µm and the mean donor endothelial graft CCT immediately after the cut was 116.5±28.7µm. At 1 month postoperatively, the mean CCT was 102.8±35.9µm. At 6 months, the mean CCT was 89.4±26.2µm. In all eyes, the mean CCT decreased from the post-cut (116.5±28.7µm) to the last visit (89.4±26.2µm) (P<0.01) due to in vivo deturgesence of the graft. We obtained 77.5% ultra-thin DSAEK immediately after the cut, 77.5% at 1 month and 89.8% after 6 months. CONCLUSION: Single-pass technique with the MORIA One Use microkeratome offers safe and reproducible DSAEK tissue preparation and allows achieving ultra-thin DSAEK in 89.8% of cases.

In vivo setup characterization for pulsed electromagnetic field exposure at 3 GHz.

An in vivo setup for pulsed electric field exposure at 3 GHz is proposed and characterized in this work. The exposure system allows far field, whole-body exposure of six animals placed in Plexiglas cages with a circular antenna. Chronic exposures under 18 W incident average power (1-4 kW peak power) and acute exposures under 56 W incident average power (4.7 kW peak power) were considered. Numerical and experimental dosimetry of the setup allowed the accurate calculation of specific absorption rate (SAR) distributions under various exposure conditions. From rat model numerical simulations, the whole-body mean SAR values were 1.3 W kg(-1) under chronic exposures and 4.1 W kg(-1) under acute exposure. The brain-averaged SAR value was 1.8 W kg(-1) and 5.7 W kg(-1) under chronic and acute exposure, respectively. Under acute exposure conditions, a 10 g specific absorption of 1.8 ± 1.1 mJ · kg(-1) value was obtained. With temperature rises below 0.8 °C, as measured or simulated on a gel phantom under typical in vivo exposures, this exposure system provides adequate conditions for in vivo experimental investigations under non-thermal conditions.

[Efficacy of corneal cross-linking for the treatment of keratoconus]. / Efficacité du cross-linking du collagène cornéen pour le traitement du kératocône.

Keratoconus (KC) is a complex disease whose pathophysiology is only partially understood. The priority in management is to halt the progression of corneal deformation as soon as possible in the course of KC disease. Corneal cross-linking (CXL) is at present the only dedicated treatment for this purpose. Its biochemical mechanism of action leads to changes in the viscoelastic properties of the cornea induced by matrix bonding and renewal of keratocytes. The effect of CXL is difficult to quantify when measured in in-vivo conditions because of a lack of consistent tools adapted for clinical practice. Nevertheless, a large amount of evidence has been collected so far confirming the positive action of CXL on corneal structural reinforcement, and numerous studies have demonstrated significant efficacy in halting progression of KC with long-term follow-up. Published studies, however, are of relatively low scientific power given the great heterogeneity of the disease and the numerous associated biases in evaluation. The purpose of this paper is to summarize the consistent evidence of efficacy of CXL and to justify its role in our therapeutic armamentarium for management of progressive KC.

Role of the phosphatidylinositol-3-kinase/Akt/target of rapamycin pathway during ambidensovirus infection of insect cells.

The phosphatidylinositol-3-kinase (PI3K)/Akt/target of rapamycin (TOR) signalling pathway controls cell growth and survival, and is targeted by a number of viruses at different phases of their infection cycle to control translation. Whether and how insect viruses interact with this pathway remain poorly addressed. Here, we investigated the role of PI3K/Akt/TOR signalling during lethal infection of insect cells with an insect parvovirus. Using Junonia coenia densovirus (JcDV; lepidopteran ambidensovirus 1) and susceptible insect cells as experimental models, we first described JcDV cytopathology, and showed that viral infection affects cell size, cell proliferation and survival. We deciphered the role of PI3K/Akt/TOR signalling in the course of infection and found that non-structural (NS) protein expression correlates with the inhibition of TOR and the shutdown of cellular synthesis, concomitant with the burst of viral protein expression. Together, these results suggest that NS proteins control the cellular translational machinery to favour the translation of viral mRNAs at the expense of cellular mRNAs. As a consequence of TOR inhibition, cell autophagy is activated. These results highlight new functions for NS proteins in the course of multiplication of an insect parvovirus.

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway.

The ubiquitin-like molecule NEDD8 is essential for viability, growth and development, and is a potential target for therapeutic intervention. We found that the small molecule inhibitor of NEDDylation, MLN4924, alters the morphology and increases the surface size of the nucleolus in human and germline cells of Caenorhabditis elegans in the absence of nucleolar fragmentation. SILAC proteomics and monitoring of rRNA production, processing and ribosome profiling shows that MLN4924 changes the composition of the nucleolar proteome but does not inhibit RNA Pol I transcription. Further analysis demonstrates that MLN4924 activates the p53 tumour suppressor through the RPL11/RPL5-Mdm2 pathway, with characteristics of nucleolar stress. The study identifies the nucleolus as a target of inhibitors of NEDDylation and provides a mechanism for p53 activation upon NEDD8 inhibition. It also indicates that targeting the nucleolar proteome without affecting nucleolar transcription initiates the required signalling events for the control of cell cycle regulators.