High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.

Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE). Results: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus. Conclusion: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.

Evaluation of Trigonella foenum-graecum L. Plant Food Safety after Lead Exposure: Phytochemical Processes.

Lead stands as a food contaminant through its accumulation in consumed plants. In this study, the effects of lead (II) chloride (PbCl2) and its levels of uptake on morphological and phytochemical responses of fenugreek were assessed to evaluate its tolerance and safety for human consumption. Results revealed that PbCl2 (50−2000 mg L−1) did not affect the germination rate, but it decreased the radicle length and amylase activity. After three months of Pb treatments, the elemental analysis showed that Pb accumulation was greater in roots than shoots, and it was not present in harvested seeds. The bioaccumulation factor > 1 and the translocation factor << 1 observed for 1000 mg L−1 PbCl2 suggested appropriateness of fenugreek as a phytostabilizer. Additionally, increased lipid peroxidation, hydrogen peroxide, flavonoid levels and catalase activity were observed in Pb-treated fenugreek. Meanwhile, decreased chlorophyll content was detected under these conditions. In turn, the total phenol was correlated with Pb treatment only in roots. HPLC analysis proved that under Pb stress, gallic acid was the most produced compound in treated roots compared to shoots, followed by quercetin. Syringic and chlorogenic acids were more produced in shoots. In conclusion, fenugreek can be used for Pb phytoremediation and is safe for consumption after Pb treatments in the traditional medicine system.

Priming with EDTA, IAA and Fe alleviates Pb toxicity in Trigonella Foneum graecum L. growth: Phytochemicals and secondary metabolites.

This study evaluated the effects of the exogenous application of ethylenediaminetetraacetic acid (EDTA), indole-3-acetic acid (IAA) and iron sulfate (FeSO4) upon the phytochemical mechanisms of fenugreek grown under Pb-excess (2000 mg L-1 PbCl2). The results showed that chemical additives of EDTA and IAA as well as FeSO4 improved fenugreek germination parameters. The radicle length and the amylase activity were significantly improved under IAA treatment compared to EDTA and FeSO4. Exogenous FeSO4 was more effective to improving growth parameters. Moreover, the decrease in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels was noted under all chemical additives especially under IAA application. In addition, it was more effective than EDTA and Fe in increasing catalase, glutathione (GSH), ascorbate peroxidase (APX), flavonoids and phenols while the increment superoxide dismutase (SOD) production was more pronounced under EDTA addition to Pb than other chelators. HPLC analysis revealed that the gallic was the major phenol produced under all chelators addition especially with IAA. In addition, the syringic acid was only produced with exogenous IAA while the quercetin was only detected under EDTA addition. Our results exhibited a higher IAA efficiency than EDTA and FeSO4 in mitigating Pb stress in fenugreek through up-regulated mechanisms of the antioxidant system for reducing reactive oxygen species (ROS) activities and enhancing special phenols.

Climatic stability, not average habitat temperature, determines thermal tolerance of subterranean beetles.

The climatic variability hypothesis predicts the evolution of species with wide thermal tolerance ranges in environments with variable temperatures, and the evolution of thermal specialists in thermally stable environments. In caves, the extent of spatial and temporal thermal variability experienced by taxa decreases with their degree of specialization to deep subterranean habitats. We use phylogenetic generalized least squares to model the relationship among thermal tolerance (upper lethal limits), subterranean specialization (estimated using ecomorphological traits), and habitat temperature in 16 beetle species of the tribe Leptodirini (Leiodidae). We found a significant, negative relationship between thermal tolerance and the degree of subterranean specialization. Conversely, habitat temperature had only a marginal effect on lethal limits. In agreement with the climatic variability hypothesis and under a climate change context, we show that the specialization process to live in deep subterranean habitats involves a reduction of upper lethal limits, but not an adjustment to habitat temperature. Thermal variability seems to exert a higher evolutionary pressure than mean habitat temperature to configure the thermal niche of subterranean species. Our results provide novel insights on thermal physiology of species with poor dispersal capabilities and on the evolutionary process of adaptation to subterranean environments. We further emphasize that the pathways determining vulnerability of subterranean species to climate change greatly depend on the degree of specialization to deep subterranean environments.

The Robot is Present: Creative Approaches for Artistic Expression With Robots.

There is growing interest in developing creative applications for robots, specifically robots that provide entertainment, companionship, or motivation. Identifying the hallmarks of human creativity and discerning how these processes might be replicated or assisted by robots remain open questions. Transdisciplinary collaborations between artists and engineers can offer insights into how robots might foster creativity for human artists and open up new pathways for designing interactive systems. This paper presents an exploratory research project centered on drawing with robots. Using an arts-led, practice-based methodology, we developed custom hardware and software tools to support collaborative drawing with an industrial robot. A team of artists and engineers collaborated over a 6-month period to investigate the creative potential of collaborative drawing with a robot. The exploratory project focused on identifying creative and collaborative processes in the visual arts, and later on developing tools and features that would allow robots to participate meaningfully in these processes. The outcomes include a custom interface for controlling and programming robot motion (EMCAR) and custom tools for replicating experimental techniques used in visual art. We report on the artistic and technical outcomes and identify key features of process-led (as opposed to outcome-led) approaches for designing collaborative and creative systems. We also consider the value of embodied and tangible interaction for artists working collaboratively with computational systems. Transdisciplinary research can help researchers uncover new approaches for designing interfaces for interacting with machines.

Effects of Light Exposure, Bottle Colour and Storage Temperature on the Quality of Malvasia delle Lipari Sweet Wine.

The influence of light exposure, bottle color and storage temperature on the quality parameters of Malvasia delle Lipari (MdL) sweet wine were investigated. Wine samples bottled in clear-colored (colorless, green and amber) glass were stored under different artificial lighting conditions, in order to simulate the retail environment (one cool-white, fluorescent lamp) and to perform an accelerated test (four and six cool-white, fluorescent lamps). The storage temperature was kept constant (25 °C) for the first 90 days of the experiment and then samples were monitored for up to 180 days at higher temperatures (30, 35 and 40 °C). The principal enological parameters, total phenols, color, 5-hydroxymethylfurfural (HMF) and 2-furaldehyde (2F) contents were studied. The shelf-life test pointed out minimum variations of the basic chemical parameters, while the quality attributes most affected by lighting were color, together with HMF and 2F levels which, hence, can be considered as indicators of the severity of storage conditions.

Exposure to Major Vector-Borne Diseases in Dogs Subjected to Different Preventative Regimens in Endemic Areas of Italy.

Vector-borne diseases (VBDs) are globally widespread arthropod-transmitted diseases with a significant impact on animal and human health. Many drivers have recently spurred the geographic spread of VBDs in dogs. This study has evaluated the exposure to most important VBDs in dogs under different preventative treatments in different regions of Italy, i.e., Veneto, Friuli Venezia-Giulia, Umbria, Giglio Island (Tuscany), Abruzzo and Latium. Serological analyses were performed to detect antibodies against Leishmania infantum, Babesia canis, Anaplasma phagocytophilum/Anaplasma platys, Ehrlichia canis/Ehrlichia ewingii, Borrelia burgdorferi, Rickettsia conorii and the circulating antigen of Dirofilaria immitis. Dogs were categorized according to the treatment schedule usually received, and the association between seropositivity and possible risk factors was statistically evaluated. Overall, 124/242 (51.2%) dogs tested positive for at least one pathogen, while 34 (14.0%) were exposed to two or more pathogens. The most detected seropositivity was against R. conorii, followed by Anaplasma spp., L. infantum, B. canis, and the other pathogens under study. Significant statistical associations were found according to geographical provenance, history of tick infestation, lifestyle and inadequate prophylactic treatments. Random/irregular treatments have been identified as a clear risk factor. These results show that adequate prophylactic treatment protocols are overlooked by dog owners, despite the availability of several effective products, with possible implications in veterinary medicine and on public health.

Active Packaging-Releasing System with Foeniculum vulgare Essential Oil for the Quality Preservation of Ready-to-Cook (RTC) Globe Artichoke Slices.

Two globe artichoke genotypes, "Spinoso sardo" and "Opera F1", have been processed as ready-to-cook (RTC) slices and refrigerated at 4 °C for 12 days (i) to evaluate the suitability to be processed as RTC slices; (ii) to evaluate the effect of a Foeniculum vulgare essential oil (EO) emitter, within an active package system, to delay quality decay, thus extending shelf life; (iii) to estimate the impact of EO emitter on the sensory profile of the RTC slices after cooking. Results revealed that both globe artichoke genotypes possess a good attitude to be processed as RTC product. "Opera F1" showed the best performances for color parameters, texture and chemical indexes, while "Spinoso sardo" showed lower mass loss (ML) over the storage time. The addition of EO emitter slowed down the consumption of O2, better preserved texture when compared to the control and more effectively control polyphenol oxidase (PPO) activity and antioxidants' retention during the cold storage. Microbial counts in control globe artichoke RTC slices were significantly higher than those packed with EO emitter, confirming the inhibiting role played by EO of F. vulgare. In addition, the EO emitter did not influence negatively the sensory profile of RTC globe artichoke slices after microwave cooking.

Packaging Solutions to Extend the Shelf Life of Green Asparagus (Asparagus officinalis L.) 'Vegalim'.

The aim of the study was to assess, through a comparative shelf-life test, the suitability of two packaging materials, namely macro-perforated polypropylene (PP MA) and micro-perforated coextruded polypropylene (PP C), for the quality preservation of green asparagus (Asparagus officinalis L. 'Vegalim'). Quality of spears was evaluated during 30 days at refrigerated storage by monitoring chemical, physical, and enzymatic parameters as well as sensory descriptors. PP C kept headspace composition close to suggested values for fresh green asparagus. Total color difference increased during the storage and it was highly correlated with chlorophyll-a and carotenoids, however, sensory color perception did not change significantly until 22 days of storage. PP C maintained ascorbic acid concentrations close to the initial levels, limited total phenolic compound loss to 24% (45% in PP MA), determined an increase of 72% in fiber content and small changes in lignin value; enzymatic changes were significantly inhibited. Significant sensorial differences were detected after 22 days of storage, with PP C performing better than PP MA. PP C film was confirmed as the best choice, limiting weight loss and maintaining a fresh-like appearance during 30 days of storage, thus allowing an extension in postharvest life.

A redefinition of the genus Troglocharinus Reitter, 1908, with description of new species (Coleoptera, Leiodidae, Cholevinae, Leptodirini).

We redefine the genus Troglocharinus Reitter, 1908 based on a phylogenetic analysis with a combination of mitochondrial and molecular data. We recovered the current Speonomites mengeli (Jeannel, 1910) and S. mercedesi (Zariquiey, 1922) as valid, separate species within the Troglocharinus clade, not directly related to Speonomites Jeannel, 1910, a finding corroborated by a detailed study of the male and female genitalia. In consequence, we reinstate Speonomus mercedesi Zariquiey, 1922 stat. nov. as a valid species, transfer both of them to the genus Troglocharinus, T. mengeli (Jeannel, 1910) comb. nov. and T. mercedesi (Zariquiey, 1922) comb. nov., and redescribe the genus. The study of new material from the distribution area of the former S. mengeli revealed the presence of two undescribed species, T. sendrai sp. nov. and T. fadriquei sp. nov., which we describe herein. We designate the lectotype of Speonomus vinyasi Escolà, 1971 to fix its identity, as among its syntypes there are two different species. In agreement with the results of the phylogenetic analyses we establish the synonymy between the genus Speonomites and Pallaresiella Fresneda, 1998 syn. nv.

Compostable Polylactide and Cellulose Based Packaging for Fresh-Cut Cherry Tomatoes: Performance Evaluation and Influence of Sterilization Treatment.

For food packaging, plastic materials display large appeal, mostly due to their versatility, mechanical, optical and barrier properties. However, they play an important role in environmental concerns and waste management issue. Compostable bioplastics represent alternative materials designed for a lower environmental impact. In this work, a biobased compostable packaging, constituted by polylactide (PLA) trays and NatureFlex™ film, was evaluated for fresh-cut cherry tomato. A comparative analysis was accomplished using traditional packaging materials, that is, polyethylene terephtalate (PET) trays and polypropylene (PP Coex) film. Structural stability under food contact conditions, mechanical and physical-chemical properties were investigated. Tensile mechanical properties, puncture resistance, contact angle (CA) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), before and after UV or radiofrequency (RF) sterilization treatment, were evaluated. UV irradiation method resulted the less invasive one. Therefore, oxygen and water vapor transmission rate (OTR and WVTR), overall chemical migration test, biodegradation assessment by biochemical oxygen demand (BOD) according to ISO 14851 and disintegration test by ISO 20200 were carried out to establish the further influence of UV sterilization on the packaging. Overall, data showed that the biobased compostable packaging for a prolonged shelf-life of fresh-cut cherry tomato has better properties that were surprisingly enhanced by the UV treatment.

Agronomical traits, phenolic compounds and antioxidant activity in raw and cooked potato tubers growing under saline conditions.

BACKGROUND: Potato yields and tuber compositions are linked to mechanisms adopted by plants to cope with salinity and often can change after cooking. The current study aimed to evaluate the effects of salinity, variety and cooking method in the composition of potato tubers. Three potato varieties (Spunta, Bellini and Alaska) grown under distinct salt levels (T1: 2.2 ms cm-1 EC, T2: 8.5 ms cm-1 EC before electromagnetic treatment and 6.3 ms cm-1 EC after electromagnetic treatment, T3: 8.5 ms cm-1 EC) were studied. Yield and tuber quality attributes (starch, dry matter, specific density and tuber size) were evaluated. Carotenoids, total and individual phenolics determined by high-performance liquid chromatography (HPLC), relative antioxidant capacity (RAC) and ions content were analyzed, in both raw and water boiled tubers. RESULTS: Tuber yield, starch, dry matter, ions and antioxidants were significantly influenced by the salinity level and variety. The least production and the highest antioxidants were obtained under T3. Antioxidants were influenced by cooking method, the interactions treatment × cooking method and variety × cooking method. Individual phenolic compounds exhibited different response to cooking as quercetin, caffeic acid and catechin decreased significantly after boiling. However, coumaric acid increased in Alaska tubers. CONCLUSION: Salinity level, variety and cooking method are important determinants of tuber yield and composition. Electromagnetic water may be useful to enhance potato production and tuber quality in areas suffering from water salinization. © 2020 Society of Chemical Industry.

Shelf-life study of ready-to-cook slices of globe artichoke 'Spinoso sardo': effects of anti-browning solutions and edible coating enriched with Foeniculum vulgare essential oil.

BACKGROUND: The globe artichoke [Cynara cardunculus var. scolymus (L.) Fiori] is a natural source of minerals, fiber, inulin, and polyphenols. A ready-to-cook (RTC) version of this product could improve its commercialization and consumption. In this study, the effects of (i) anti-browning treatments (citric acid 0.5% + ascorbic acid 2%, or cysteine 0.5%, w/v) and (ii) dipping in locust bean gum (LBG) edible coating with or without Foeniculum vulgare essential oil (EO) were evaluated on RTC globe artichoke slices cv. 'Spinoso sardo' during storage (11 days at 4 °C). Fresh weight loss, color, texture, polyphenol oxidase (PPO), microbiological and chemical parameters, antioxidant capacity, and sensory descriptors were determined. RESULTS: The results showed that, despite the antioxidant treatment used, when EO was added to LBG, all microbiological groups underwent an average reduction of 0.50 log CFU g-1 . Cysteine preserved the antioxidant capacity, color, and texture of samples better than citric acid and ascorbic acid, and inhibited PPO; the addition of EO to LBG enhanced these effects. At the end of the storage period, the overall highest sensory attribute score was attained by the coated globe artichoke samples with EO. CONCLUSION: The marked efficacy of the LBG edible coating with added F. vulgare EO in maintaining microbiological, physical, chemical, and sensory qualities makes it a promising processing tool for the preservation of ready-to-cook Spinoso sardo globe artichoke slices during storage for 11 days at 4 °C. © 2019 Society of Chemical Industry.

Contribution of Blood Orange-Based Beverages to Bioactive Compounds Intake.

The study aimed at screening the levels of ascorbic acid, hydroxycinnamic acids (HCAs) and total anthocyanins in commercial beverages containing blood orange juice (BOJ), estimating the contribution of these products to the intake of health-promoting compounds and at discussing the actual value of the products on a price/bioactive level basis. Results demonstrate that the reference to BOJ in many beverages is misleading, as inferred from the very low bioactive levels observed. These beverages, in label should refer as "water-based" instead of "fruit-based beverage." Accordingly, the intake of bioactives from BOJ-based beverages, with the exception of ascorbic acid used in the most cases as preservative, is often very low. The intake of bioactive components from blood orange consumption is much higher compared to the consumption of BOJ-based beverages, hence the consumption of blood oranges and 100% BOJs should be preferred in order to guarantee the intake of a rich pool of bioactive compounds. Finally, the market value of BOJ-based beverages is not correlated with their real nutritional value: the relative unitary cost of the three classes of bioactive compounds considered increased in the order: fresh blood oranges < 100% BOJ < BOJ-based beverages. Hence, the consumption of fresh blood oranges represents the cheapest way to ensure the intake of health-promoting bioactive compounds such as anthocyanins and HCAs.

Targeted secondary metabolic and physico-chemical traits analysis to assess genetic variability within a germplasm collection of "long storage" tomatoes.

"Long storage" tomato is a crop traditionally cultivated in the Mediterranean area under no water supply, that recently has attracted the interest of breeders for its high tolerance to drought and as potential genetic source in breeding programs for water stress resistance. A collection of 28 genotypes of "long storage" tomato (Solanum lycopersicum L.) was studied for carotenoid and polyphenol profile and content, vitamin C, and other physico-chemical traits of fruits. Tomato carotenoids and polyphenols were identified and quantified using high-performance liquid chromatography coupled with diode array detection and electrospray-mass spectrometry (HPLC/DAD/ESI-MS); nineteen different phenolic compounds and six different carotenoids, for a total of 25 markers, have been detected, quantified and used to discriminate among the different landraces to find out which could be the best candidate for a medium-to-large scale cultivation. Different statistical approaches (ANOVA, Principal Components Analysis, Cluster Analysis) have been used for data analysis.

Thermal niche estimators and the capability of poor dispersal species to cope with climate change.

For management strategies in the context of global warming, accurate predictions of species response are mandatory. However, to date most predictions are based on niche (bioclimatic) models that usually overlook biotic interactions, behavioral adjustments or adaptive evolution, and assume that species can disperse freely without constraints. The deep subterranean environment minimises these uncertainties, as it is simple, homogeneous and with constant environmental conditions. It is thus an ideal model system to study the effect of global change in species with poor dispersal capabilities. We assess the potential fate of a lineage of troglobitic beetles under global change predictions using different approaches to estimate their thermal niche: bioclimatic models, rates of thermal niche change estimated from a molecular phylogeny, and data from physiological studies. Using bioclimatic models, at most 60% of the species were predicted to have suitable conditions in 2080. Considering the rates of thermal niche change did not improve this prediction. However, physiological data suggest that subterranean species have a broad thermal tolerance, allowing them to stand temperatures never experienced through their evolutionary history. These results stress the need of experimental approaches to assess the capability of poor dispersal species to cope with temperatures outside those they currently experience.

Effects of processing on the polyphenol and phenolic acid content and antioxidant capacity of semi-dried cherry tomatoes (Lycopersicon esculentum M.).

BACKGROUND: This study was performed to test the effects of pre-treating cherry tomatoes with a solution containing citric acid-NaCl-CaCl2 (10:10:24 g L(-1)), followed by one of three different drying regimes (40, 60, 80 °C) on the antioxidant capacity of their aqueous extracts and the extent of phenolic compound degradation. RESULTS: Chlorogenic acids, caffeic acid, ferulic acid, rutin and naringenin were all detected in the aqueous extracts. In fresh cherry tomatoes the predominant phenolic compound was rutin, followed by naringenin, which corresponded to 79% and 8% of the total phenolic compounds present, respectively. Pre-treatment was protective towards naringenin and had a modest protective effect on rutin and ferulic acid (0.1 > P > 0.05). Total phenolic content was similar in all samples, but there was a trend for the level of free polyphenols to be lower in treated tomatoes. The destruction of naringenin was confirmed by liquid chromatographic-mass spectrometric data. CONCLUSION: A significant effect of temperature on the antioxidant capacity was observed. After this treatment the industry might introduce some advances in the processing of tomatoes, preserving the main nutritive characteristics and saving the products as semi-dried.

Lack of evolutionary adjustment to ambient temperature in highly specialized cave beetles.

BACKGROUND: A key question in evolutionary biology is the relationship between species traits and their habitats. Caves offer an ideal model to test the adjustment of species to their surrounding temperature, as they provide homogeneous and simple environments. We compared two species living under different thermal conditions within a lineage of Pyrenean beetles highly modified for the subterranean life since the Miocene. One, Troglocharinus fonti, is found in caves at 4-11°C in the ancestral Pyrenean range. The second, T. ferreri, inhabits the coastal area of Catalonia since the early Pliocene, and lives at 14-16°C. RESULTS: We found no differences in their short term upper thermal limit (ca. 50°C), similar to that of most organisms, or their lower thermal limit (ca. -2.5°C), higher than for most temperate insects and suggesting the absence of cryoprotectants. In longer term tests (7 days) survival between 6-20°C was almost 100% for both species plus two outgroups of the same lineage, but all four died between 23-25°C, without significant differences between them. CONCLUSIONS: Our results suggest that species in this lineage have lost some of the thermoregulatory mechanisms common in temperate insects, as their inferred default tolerance range is larger than the thermal variation experienced through their whole evolutionary history.

The increase in maternal expression of axin1 and axin2 contribute to the zebrafish mutant ichabod ventralized phenotype.

ß-Catenin is a central effector of the Wnt pathway and one of the players in Ca(+)-dependent cell-cell adhesion. While many wnts are present and expressed in vertebrates, only one ß-catenin exists in the majority of the organisms. One intriguing exception is zebrafish that carries two genes for ß-catenin. The maternal recessive mutation ichabod presents very low levels of ß-catenin2 that in turn affects dorsal axis formation, suggesting that ß-catenin1 is incapable to compensate for ß-catenin2 loss and raising the question of whether these two ß-catenins may have differential roles during early axis specification. Here we identify a specific antibody that can discriminate selectively for ß-catenin1. By confocal co-immunofluorescent analysis and low concentration gain-of-function experiments, we show that ß-catenin1 and 2 behave in similar modes in dorsal axis induction and cellular localization. Surprisingly, we also found that in the ich embryo the mRNAs of the components of ß-catenin regulatory pathway, including ß-catenin1, are more abundant than in the Wt embryo. Increased levels of ß-catenin1 are found at the membrane level but not in the nuclei till high stage. Finally, we present evidence that ß-catenin1 cannot revert the ich phenotype because it may be under the control of a GSK3ß-independent mechanism that required Axin's RGS domain function.

Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma.

Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT.   Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.