Role of astrocyte senescence regulated by the non- canonical autophagy in the neuroinflammation associated to cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is a fatal neuroinflammatory syndrome caused (in humans) by the protozoa Plasmodium (P.) falciparum. Glial cell activation is one of the mechanisms that contributes to neuroinflammation in CM. RESULT: By studying a mouse model of CM (caused by P. berghei ANKA), we describe that the induction of autophagy promoted p21-dependent senescence in astrocytes and that CXCL-10 was part of the senescence-associated secretory phenotype. Furthermore, p21 expression was observed in post-mortem brain and peripheral blood samples from patients with CM. Lastly, we found that the depletion of senescent astrocytes with senolytic drugs abrogated inflammation and protected mice from CM. CONCLUSION: Our data provide evidence for a novel mechanism through which astrocytes could be involved in the neuropathophysiology of CM. p21 gene expression in blood cell and an elevated plasma CXCL-10 concentration could be valuable biomarkers of CM in humans. In the end, we believe senolytic drugs shall open up new avenues to develop newer treatment options.

CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway.

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of in vivo and in vitro approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, p16 overexpression was associated with triglyceride accumulation and increased lipid droplet numbers in vitro, and decreased ketogenesis and hepatic mitochondrial activity in vivo Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between CDKN2A expression and PPARA and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility.

Consumption rituals relating to food and drink: A review and research agenda.

Rituals are common in relation to consumption of food and drink, and are related to psychosocial benefits such as social bonding, affective change, and enhanced consumer perceptions. However, theoretical understanding of food and drink consumption rituals, and empirical examination of their effects and mechanisms of action, is limited. In this literature review we show a need for greater theoretical understanding of these rituals, and especially mechanisms linking ritual performance to outcomes. Such understanding would be greatly enhanced by a holistic model of consumption ritual and the development of an instrument that can be used to study different aspects of such rituals, both of which are currently lacking. We also highlight specific research questions regarding the cognitive, social, and affective outcomes of ritual consumption of food and drink, and the affective and cognitive-behavioural mechanisms that might precede them. We provide suggestions regarding the research paradigms and methods that might suit such questions, and encourage research along these lines of inquiry.

Vertical bone augmentation in a single-tooth gap with an allogenic bone ring: Clinical considerations.

OBJECTIVE: The main objective of this case report is to introduce a one-stage bone block augmentation with a cylindrical freeze-dried bone allograft (FDBA) and simultaneous implantation for the reconstruction of a single-tooth bone defect. CLINICAL CONSIDERATIONS: The report describes this method on the basis of radiographical and clinical images derived from a single patient. CONCLUSIONS: The report demonstrates the time-saving and successful application of this treatment concept, which has the potential to increase patient satisfaction and comfort. CLINICAL SIGNIFICANCE: The application of the presented technique enabled a prosthetic rehabilitation of the extracted tooth about 3 months earlier as compared to the conventional procedure, while demonstrating no compromises regarding clinical outcome, functionality and esthetics.

Influence of BMI and dietary restraint on self-selected portions of prepared meals in US women.

The rise of obesity prevalence has been attributed in part to an increase in food and beverage portion sizes selected and consumed among overweight and obese consumers. Nevertheless, evidence from observations of adults is mixed and contradictory findings might reflect the use of small or unrepresentative samples. The objective of this study was i) to determine the extent to which BMI and dietary restraint predict self-selected portion sizes for a range of commercially available prepared savoury meals and ii) to consider the importance of these variables relative to two previously established predictors of portion selection, expected satiation and expected liking. A representative sample of female consumers (N = 300, range 18-55 years) evaluated 15 frozen savoury prepared meals. For each meal, participants rated their expected satiation and expected liking, and selected their ideal portion using a previously validated computer-based task. Dietary restraint was quantified using the Dutch Eating Behaviour Questionnaire (DEBQ-R). Hierarchical multiple regression was performed on self-selected portions with age, hunger level, and meal familiarity entered as control variables in the first step of the model, expected satiation and expected liking as predictor variables in the second step, and DEBQ-R and BMI as exploratory predictor variables in the third step. The second and third steps significantly explained variance in portion size selection (18% and 4%, respectively). Larger portion selections were significantly associated with lower dietary restraint and with lower expected satiation. There was a positive relationship between BMI and portion size selection (p = 0.06) and between expected liking and portion size selection (p = 0.06). Our discussion considers future research directions, the limited variance explained by our model, and the potential for portion size underreporting by overweight participants.

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, ß = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, ß = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.

Prompts to eat novel and familiar fruits and vegetables in families with 1-3 year-old children: Relationships with food acceptance and intake.

Toddlers often go through a picky eating phase, which can make it difficult to introduce new foods into the diet. A better understanding of how parents' prompts to eat fruits and vegetables are related to children's intake of these foods will help promote healthy eating habits. 60 families recorded all toddler meals over one day, plus a meal in which parents introduced a novel fruit/vegetable to the child. Videos were coded for parent and child behaviors. Parents completed a feeding style questionnaire and three 24-h dietary recalls about their children's intake. Parents made, on average, 48 prompts for their children to eat more during the main meals in a typical day, mostly of the neutral type. Authoritarian parents made the most prompts, and used pressure the most often. In the novel food situation, it took an average of 2.5 prompts before the child tasted the new food. The most immediately successful prompt for regular meals across food types was modeling. There was a trend for using another food as a reward to work less well than a neutral prompt for encouraging children to try a novel fruit or vegetable. More frequent prompts to eat fruits and vegetables during typical meals were associated with higher overall intake of these food groups. More prompts for children to try a novel vegetable was associated with higher overall vegetable intake, but this pattern was not seen for fruits, suggesting that vegetable variety may be more strongly associated with intake. Children who ate the most vegetables had parents who used more "reasoning" prompts, which may have become an internalized motivation to eat these foods, but this needs to be tested explicitly using longer-term longitudinal studies.

Brain dynamics of meal size selection in humans.

Although neuroimaging research has evidenced specific responses to visual food stimuli based on their nutritional quality (e.g., energy density, fat content), brain processes underlying portion size selection remain largely unexplored. We identified spatio-temporal brain dynamics in response to meal images varying in portion size during a task of ideal portion selection for prospective lunch intake and expected satiety. Brain responses to meal portions judged by the participants as 'too small', 'ideal' and 'too big' were measured by means of electro-encephalographic (EEG) recordings in 21 normal-weight women. During an early stage of meal viewing (105-145 ms), data showed an incremental increase of the head-surface global electric field strength (quantified via global field power; GFP) as portion judgments ranged from 'too small' to 'too big'. Estimations of neural source activity revealed that brain regions underlying this effect were located in the insula, middle frontal gyrus and middle temporal gyrus, and are similar to those reported in previous studies investigating responses to changes in food nutritional content. In contrast, during a later stage (230-270 ms), GFP was maximal for the 'ideal' relative to the 'non-ideal' portion sizes. Greater neural source activity to 'ideal' vs. 'non-ideal' portion sizes was observed in the inferior parietal lobule, superior temporal gyrus and mid-posterior cingulate gyrus. Collectively, our results provide evidence that several brain regions involved in attention and adaptive behavior track 'ideal' meal portion sizes as early as 230 ms during visual encounter. That is, responses do not show an increase paralleling the amount of food viewed (and, in extension, the amount of reward), but are shaped by regulatory mechanisms.

Electromigrative separation techniques in forensic science: combining selectivity, sensitivity, and robustness.

In this review we introduce the advantages and limitations of electromigrative separation techniques in forensic toxicology. We thus present a summary of illustrative studies and our own experience in the field together with established methods from the German Federal Criminal Police Office rather than a complete survey. We focus on the analytical aspects of analytes' physicochemical characteristics (e.g. polarity, stereoisomers) and analytical challenges including matrix tolerance, separation from compounds present in large excess, sample volumes, and orthogonality. For these aspects we want to reveal the specific advantages over more traditional methods. Both detailed studies and profiling and screening studies are taken into account. Care was taken to nearly exclusively document well-validated methods outstanding for the analytical challenge discussed. Special attention was paid to aspects exclusive to electromigrative separation techniques, including the use of the mobility axis, the potential for on-site instrumentation, and the capillary format for immunoassays. The review concludes with an introductory guide to method development for different separation modes, presenting typical buffer systems as starting points for different analyte classes. The objective of this review is to provide an orientation for users in separation science considering using capillary electrophoresis in their laboratory in the future.

Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts.

Cyclooxygenase 2 and release of prostaglandin E2 are involved in many responses including inflammation and are upregulated during cellular senescence. However, little is known about the role of lipid inflammatory mediators in senescence. Here, we investigated the mechanism by which the COX-2/PGE2 axis induces senescence. Using the NS398 specific inhibitor of COX-2, we provide evidence that reactive oxygen species by-produced by the COX-2 enzymatic activity are negligible in front of the total senescence-associated oxidative stress. We therefore investigated the role of PGE2 by invalidating the PGE2 synthases downstream of COX-2, or the specific PGE2 receptors, or by applying PGE2 or specific agonists or antagonists. We evaluated the effect on senescence by evaluating the senescence-associated proliferation arrest, the percentage of senescence-associated beta-galactosidase-positive cells, and the expression of senescent molecular markers such as IL-6 and MCP1. We show that PGE2 acting on its EP specific receptors is able to induce both the onset of senescence and the maintenance of the phenotype. It did so only when the PGE2/lactate transporter activity was enhanced, indicating that PGE2 acts on senescence more via the pool of intracellular EP receptors than via those localized at the cell surface. Treatment with agonists, antagonists and silencing of the EP receptors by siRNA revealed that EP3 was the most involved in transducing the intracrine effects of PGE2. Immunofluorescence experiments confirmed that EP3 was more localized in the cytoplasm than at the cell surface. Taken together, these results suggest that COX-2 contributes to the establishment and maintenance of senescence of normal human fibroblasts via an independent-ROS and a dependent-PGE2/EPs intracrine pathway.

Identification of a gene signature of a pre-transformation process by senescence evasion in normal human epidermal keratinocytes.

BACKGROUND: Epidemiological data show that the incidence of carcinomas in humans is highly dependent on age. However, the initial steps of the age-related molecular oncogenic processes by which the switch towards the neoplastic state occurs remain poorly understood, mostly due to the absence of powerful models. In a previous study, we showed that normal human epidermal keratinocytes (NHEKs) spontaneously and systematically escape from senescence to give rise to pre-neoplastic emerging cells. METHODS: Here, this model was used to analyze the gene expression profile associated with the early steps of age-related cell transformation. We compared the gene expression profiles of growing or senescent NHEKs to post-senescent emerging cells. Data analyses were performed by using the linear modeling features of the limma package, resulting in a two-sided t test or F-test based on moderated statistics. The p-values were adjusted for multiple testing by controlling the false discovery rate according to Benjamini Hochberg method.The common gene set resulting of differential gene expression profiles from these two comparisons revealed a post-senescence neoplastic emergence (PSNE) gene signature of 286 genes. RESULTS: About half of these genes were already reported as involved in cancer or premalignant skin diseases. However, bioinformatics analyses did not highlight inside this signature canonical cancer pathways but metabolic pathways, including in first line the metabolism of xenobiotics by cytochrome P450. In order to validate the relevance of this signature as a signature of pretransformation by senescence evasion, we invalidated two components of the metabolism of xenobiotics by cytochrome P450, AKR1C2 and AKR1C3. When performed at the beginning of the senescence plateau, this invalidation did not alter the senescent state itself but significantly decreased the frequency of PSNE. Conversely, overexpression of AKR1C2 but not AKR1C3 increased the frequency of PSNE. CONCLUSIONS: To our knowledge, this study is the first to identify reprogrammation of metabolic pathways in normal keratinocytes as a potential determinant of the switch from senescence to pre-transformation.

[Sorting of senescent cells by flow cytometry: Specificities and pitfalls to avoid]. / Tri des cellules sénescentes par cytométrie en flux - Des spécificitéset des pièges à éviter.

Cells can be reprogrammed into senescence to adapt to a variety of stresses, most often affecting the genome integrity. Senescent cells accumulate with age or upon various insults in almost all tissues, and contribute to the development of several age-associated pathologies. Studying the molecular pathways involved in senescence induction, maintenance, or escape is challenged by the heterogeneity in the level of commitment to senescence, and by the pollution of senescent cell populations by proliferating pre- or post-senescent cells. We coped with these difficulties by developing a protocol for sorting senescent cells by flow cytometry, based on three major senescence markers : the SA-ß-Galactosidase activity, the size of the cells, and their granularity reflecting the accumulation of aggregates, lysosomes, and altered mitochondria. We address the issues related to sorting senescent cells, the pitfalls to avoid, and propose solutions for sorting viable cells expressing senescent markers at different extents.

Title: Tri des cellules sénescentes par cytométrie en flux - Des spécificitéset des pièges à éviter. Abstract: La sénescence est un état d'adaptation des cellules au stress qui contribue au vieillissement et au développement de nombreuses maladies. Étudier les voies moléculaires modulant l'induction, le maintien ou l'échappement de la sénescence est compliqué par la contamination des populations de cellules sénescentes par des cellules proliférantes pré- ou post-sénescentes. Pour contourner cette difficulté, nous avons développé un protocole de tri par cytométrie en flux, fondé sur trois marqueurs majeurs de sénescence (l'activité SA-ß-galactosidase, la taille et la granularité des cellules), qui permet de trier des cellules sénescentes viables, à des degrés choisis d'engagement dans le phénotype.

A lack of appetite for information and computation. Simple heuristics in food choice.

The predominant, but largely untested, assumption in research on food choice is that people obey the classic commandments of rational behavior: they carefully look up every piece of relevant information, weight each piece according to subjective importance, and then combine them into a judgment or choice. In real world situations, however, the available time, motivation, and computational resources may simply not suffice to keep these commandments. Indeed, there is a large body of research suggesting that human choice is often better accommodated by heuristics-simple rules that enable decision making on the basis of a few, but important, pieces of information. We investigated the prevalence of such heuristics in a computerized experiment that engaged participants in a series of choices between two lunch dishes. Employing MouselabWeb, a process-tracing technique, we found that simple heuristics described an overwhelmingly large proportion of choices, whereas strategies traditionally deemed rational were barely apparent in our data. Replicating previous findings, we also observed that visual stimulus segments received a much larger proportion of attention than any nutritional values did. Our results suggest that, consistent with human behavior in other domains, people make their food choices on the basis of simple and informationally frugal heuristics.

Life Cycle Assessment of Reusable and Disposable Cystoscopes: A Path to Greener Urological Procedures.

BACKGROUND: The environmental impact of reusable and disposable devices is unclear; reuse is expected to reduce the carbon footprint, but the environmental impact of reprocessing of reusable devices is increasingly being questioned. OBJECTIVE: The aim was to provide the first rigorous life cycle assessment of reusable and disposable flexible cystoscopes. DESIGN, SETTING, AND PARTICIPANTS: We performed a life cycle assessment of reusable flexible cystoscopes and the aS4C single-use cystoscope (aScope; Ambu, Ballerup, Denmark). For the aScope, the complete lifespan of the scope was evaluated, including raw material extraction, material formulation, component production, product assembly, distribution, transportation after use, and final disposal. For reusable cystoscopes, we limited our analysis to their reprocessing, using a model consisting of standard high-level disinfection with peracetic acid. The environmental impact was evaluated by an independent third-party consulting company APESA (Technopole Hélioparc, Pau, France) dedicated to such risk assessments. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The environmental footprint of both cystoscopes was assessed using five environmental impact categories, namely, climate change, mineral resource depletion, ecotoxicity, acidification, and eutrophication. To perform the life cycle assessment, Simapro v9.3.3 software was used and the Ecoinvent v3.5 database was employed as the primary life cycle inventory database. A Monte Carlo analysis was used to account for the inherent uncertainty in life cycle inventory data and the variability in material and energy consumption for each type of flexible cystoscope. RESULTS AND LIMITATIONS: By only comparing the disinfection reprocessing of reusable cystoscopes with the complete lifespan of the single-use cystoscope, the use of the aScope would allow a reduction of at least 33% in the climate change category, 50% in the mineral resources' depletion category, 51% in the ecotoxicity category, 71% in the acidification category, and 49% in the eutrophication category. Our results cannot be generalized to all health care facilities as we studied only one type of reprocessing method and one disposable flexible cystoscope. CONCLUSIONS: Disinfection reprocessing of reusable cystoscopes was found to have a significantly larger environmental footprint and impact than the whole lifespan of the single-use cystoscope aScope. PATIENT SUMMARY: Using a cradle-to-grave life cycle analysis, we showed that the environmental footprint of a flexible cystoscopy procedure can be reduced by using a disposable cystoscope instead of a reusable cystoscope.

The NLRP6 protein is very faintly expressed in several normal and cancerous epithelial cells and may be confused with an unrelated protein.

Nod-Like Receptor Pyrin domain-containing protein 6 (NLRP6), a member of the Nucleotide-oligomerization domain-Like Receptor (NLR) family of proteins, assembles together with the ASC protein to form an inflammasome upon stimulation by bacterial lipoteichoic acid and double-stranded DNA. Besides its expression in myeloid cells, NLRP6 is also expressed in intestinal epithelial cells where it may contribute to the maintenance of gut homeostasis and negatively controls colorectal tumorigenesis. Here, we report that NLRP6 is very faintly expressed in several colon cancer cell lines, detected only in cytoplasmic small dots were it colocalizes with ASC. Consequently, it is very hardly detected by standard western-blotting techniques by several presently available commercial antibodies which, in contrast, highly cross-react with a protein of 90kDa that we demonstrate to be unrelated to NLRP6. We report here these results to caution the community not to confuse the 90kDa protein with the endogenous human NLRP6.

Flow Cytometry-based Method for Efficient Sorting of Senescent Cells.

Cellular senescence is a reprogrammed cell state triggered as an adaptative response to a variety of stresses, most often those affecting the genome integrity. Senescent cells accumulate in most tissues with age and contribute to the development of several pathologies. Studying molecular pathways involved in senescence induction and maintenance, or in senescence escape, can be hindered by the heterogeneity of senescent cell populations. Here, we describe a flow cytometry strategy for sorting senescent cells according to three senescence canonical markers whose thresholds can be independently adapted to be more or less stringent: (i) the senescence-associated-ß-galactosidase (SA-ß-Gal) activity, detected using 5-dodecanoylaminofluorescein Di-ß-D-galactopyranoside (C12FDG), a fluorigenic substrate of ß-galactosidase; (ii) cell size, proportional to the forward scatter value, since increased size is one of the major changes observed in senescent cells; and (iii) cell granularity, proportional to the side scatter value, which reflects the accumulation of aggregates, lysosomes, and altered mitochondria in senescent cells. We applied this protocol to the sorting of normal human fibroblasts at the replicative senescence plateau. We highlighted the challenge of sorting these senescent cells because of their large sizes, and established that it requires using sorters equipped with a nozzle of an unusually large diameter: at least 200 µm. We present evidence of the sorting efficiency and sorted cell viability, as well as of the senescent nature of the sorted cells, confirmed by the detection of other senescence markers, including the expression of the CKI p21 and the presence of 53BP1 DNA damage foci. Our protocol makes it possible, for the first time, to sort senescent cells from contaminating proliferating cells and, at the same time, to sort subpopulations of senescent cells featuring senescent markers to different extents. Graphical abstract.

Senescence Induced by UVB in Keratinocytes Impairs Amino Acids Balance.

Skin is one of the most exposed organs to external stress. Namely, UV rays are the most harmful stress that could induce important damage leading to skin aging and cancers. At the cellular level, senescence is observed in several skin cell types and contributes to skin aging. However, the origin of skin senescent cells is still unclear but is probably related to exposure to stresses. In this work, we developed an in vitro model of UVB-induced premature senescence in normal human epidermal keratinocytes. UVB-induced senescent keratinocytes display a common senescent phenotype resulting in an irreversible cell cycle arrest, an increase in the proportion of senescence-associated ß-galactosidase‒positive cells, unrepaired DNA damage, and a long-term DNA damage response activation. Moreover, UVB-induced senescent keratinocytes secrete senescence-associated secretory phenotype factors that influence cutaneous squamous cell carcinoma cell migration. Finally, a global transcriptomic study highlighted that senescent keratinocytes present a decrease in the expression of several amino acid transporters, which is associated with reduced intracellular levels of glycine, alanine, and leucine. Interestingly, the chemical inhibition of the glycine transporter SLC6A9/Glyt1 triggers senescence features.

Nonaqueous capillary electrophoresis-mass spectrometry: a versatile, straightforward tool for the analysis of alkaloids from psychoactive plant extracts.

In this study we show that a nonaqueous capillary electrophoresis mass spectrometry (NACE-MS) method carefully optimized by a design of experiment can be applied to a very large number of alkaloids in different plant extracts. It is possible to characterize the pattern of the psychoactive alkaloids in several plant samples and preparations thereof, each presenting different challenges in their analysis. The method is shown to be able to separate structurally closely related substances, diastereomers and further isobaric compounds, to separate members of different alkaloid classes within one run and to tolerate significant matrix load. A comparison with methods presented in the literature reveals that a near-generic NACE-MS method for the fast profiling of alkaloids in forensically relevant plant samples has been developed.

Cost and Environmental Impact of Disposable Flexible Cystoscopes Compared to Reusable Devices.

Objectives: To quantify the environmental impact and costs associated with flexible cystoscopy procedures from an institutional perspective, with particular attention for the comparison between disposable and reusable cystoscopes. Materials and Methods: This is a single-center retrospective study, including all flexible cystoscopies performed between 2020 and 2021 using reusable or single-use devices. The Ambu aS4C single-use cystoscope (Ballerup, Denmark) gradually replaced the reusable device in our center, with exclusive use from October 2021. Reprocessing costs for reusable cystoscopes were evaluated using a micro-costing approach. The environmental impact of reusable and disposable cystoscopes was assessed by the amount of waste and water consumed for each procedure. Results: A total of 1578 flexible cystoscopies using reusable cystoscopes were performed in 2020, and 550 cystoscopies were performed using the Ambu aS4C cystoscope from October 2021 to February 2022. The cost of flexible cystoscopy with a reusable and a disposable endoscope was €196 and €192, respectively. The amount of waste generated by reprocessing reusable and disposable cystoscopes was 800 and 200 g per procedure, respectively. Water consumption for sterilization of the reusable cystoscope was 60 L per procedure, whereas no water consumption was required with the Ambu aS4C cystoscope. A 100% Ambu aS4C cystoscope use would reduce waste generation and water consumption by 946.8 kg and 94.68 m3 per year. Conclusion: In this study, implementing a strategy of using 100% disposable cystoscopes was associated with similar costs and reduced waste generation and water consumption compared to reusable devices. Future studies are needed to compare the carbon footprint of these devices, through a comprehensive and rigorous life cycle assessment from manufacturing to recycling.

The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion.

A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1-40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient's treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention.