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We propose a hybrid approach based on meta-modelling techniques and machine-learning algorithms to determine the best car configuration for each circuit. By a specific interpolation model, we obtain an accurate estimation of the car’s speed as a function of the front wing configuration and the bend curvature. Some high-fidelity fluid dynamic simulations train the model and extend it to the entire design space. These data are then used as input for a simplified car dynamics model, providing an accurate estimate of the ideal lap time. Comparison with actual telemetry data confirms that the resulting tool is reliable, fast and easy to use.

Cycling infrastructures contribute to advancing zero-impact transport systems, aligning with the European Commission’s proactive climate change mitigation policies. This paper explores the potential of innovative and sustainable pavements for cycling paths with mixtures composed of road-milling materials. This investigation involves low-environmental-impact bituminous-based mixtures differing from recipe, mixing method, and laying. Up to 100% secondary aggregates are used as alternative materials to design the Grande Raccordo Anulare delle Biciclette (GRAB), a 44-km cycling ring in Rome. According to the European standard EN 15804, their “from cradle to gate” life cycle analysis allows a comprehensive assessment and comparison of the environmental impact. Core and additional environmental impact categories and resource use indicators were quantified using primary data from asphalt producers and secondary data from the Ecoinvent database in the SimaPro software. Within the H2020 InfraROB project (grant agreement no. 955337), which aims at enhancing road infrastructure integrity, performance, and safety through autonomous robotic solutions and modularization, experimental sections have been constructed using a cold-mixed asphalt composed entirely of recycled asphalt and a rejuvenating additive. The results underscore the potential of the examined low-impact approach in conserving Earth’s resources, ensuring long-lasting infrastructure for vulnerable urban populations and fostering sustainable environmental management.

The daily incorporation of music education and instrumental practice within school settings has been linked to various advantages, such as enhanced language skills and improved peer relationships. Mastering musical skills poses a significant challenge, necessitating proper teaching activities and adherence to specific learning theories. The rapid evolution of technology has emerged as a powerful tool for improving musical education. Nevertheless, crafting technology aligned with specific learning theories, including appropriate educational materials, remains a formidable task. Likewise, music teachers grapple with the challenge of seamlessly integrating technology into their teaching activities without robust support. This paper delves into this challenge, presenting the results from CrazySquare, a project that mainly focuses on guitar musical learning. It leverages the Technological Pedagogical Content Knowledge (TPACK) framework to enable the effective integration of technology into traditional teaching practices for Italian school-age pre-adolescents. The fruitfulness of using the TPACK framework is strengthened since it has been carried out through the Technology Enhanced Learning-oriented User-Centered Design methodology. This methodology inherently necessitates a multidisciplinary team at the core of the design process, and it has an iterative nature encompassing both expert-based and end-user-based evaluation steps. Such an approach can promote the controlled diffusion of technology in education as a scaffold for learning, reducing the barriers typically faced by teachers and students in the digital era.

Background: Over the last two decades, many elective procedures have transitioned to day-case surgery thanks to the introduction of ‘enhanced recovery’ protocols. Only recently has total hip arthroplasty been considered a candidate for day-case surgery, as it was once associated with significant pain, mobility impairment and prolonged postoperative recovery. The National Orthopaedic Hospital Cappagh became the first public hospital in Ireland to set up a day-case total hip arthroplasty service in June 2018, and since then has performed over 109 such cases.Aims: We outline our day-case total hip arthroplasty pathway, with specific focus on anaesthetic considerations. We report rates of failed discharge and readmissionResults: We achieved successful same-day discharge in 90.8% of our first 109 cases. Readmission rate was 4.6%.Conclusion: Our experience of implementing a day-case total hip arthroplasty pathway was highly positive and congruent with expectations from the literature. With appropriate patient selection and education, day-case total hip arthroplasty is not just safe, but of benefit to both patients and healthcare systems.

(Abstracted from Am J Obstet Gynecol2023;229(4):377–387Electronic fetal monitoring is used on more than 3.8 million parturients a year. Despite its ubiquitous use, fetal heart rate tracing (FHRT) is marred by intraobserver variability and inconsistent use of terms to describe contraction patterns.

ABSTRACTThe Italian public administration was called upon to spend the largest proportion of the funds made available by the European Union within the framework of the post-pandemic economic recovery programme NextGeneration EU. At the end of 2022, implementation delays drew the attention of the new ruling coalition led by Giorgia Meloni to the lack of administrative capacity, a risk factor that the Italian National Recovery and Resilience Plan had foreseen – to the extent that it had included within it a number of reforms of the public administration. The article analyses the outcomes of the steps taken to increase administrative capacity in accordance with the Plan. It highlights that EU funds are out of all proportion to the actual capacity of Italian authorities to spend them.

In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide. We now show that the dark process is not limited to the unusual structural molecule melanin: signaling biomolecules such as indolamine and catecholamine neurotransmitters and hormones can also be chemiexcited to energy levels high enough to form dCPDs. Oxidation of serotonin, dopamine, melatonin, and related biogenic amines by peroxynitrite created triplet-excited species, evidenced by chemiluminescence, energy transfer to a triplet-state reporter, or transfer to O2resulting in singlet molecular oxygen. For a subset of these signaling molecules, triplet states created by peroxynitrite or peroxidase generated dCPDs at levels comparable to ultraviolet (UV). Neurotransmitter catabolism by monoamine oxidase also generated dCPDs. These results reveal a large class of signaling molecules as electronically excitable by biochemical reactions and thus potential players in deviant mammalian metabolism in the absence of light.

ABSTRACTIntroductionOvarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting.Areas coveredThis review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting.Expert opinionProtein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.

ABSTRACTIntroductionLimited data on the role of pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer are available.Areas coveredThis article aims to provide an overview of the current treatment options for patients with vulvar cancer. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Science databases, as well as ClinicalTrials.gov were searched to review the current evidence as well as future perspectives on the role of pharmacotherapy in patients with vulvar carcinoma.Expert opinionThere has been no consensus on the pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer. Concurrent platinum-based chemoradiation is the most widely used treatment modality for primary treatment or for neoadjuvant settings. Chemotherapy in metastatic disease is considered a palliative treatment. Anti-EGFR tyrosine kinase inhibitors seem to show promising anti-tumor activity in patients harboring EGFR alteration. Similarly, growing evidence supports the adoption of immune checkpoint inhibitors in both neoadjuvant and metastatic settings. Molecular and genomic profiling is advocated to identify target mutations. The PI3K/AKT/mTORand HER/ErbBpathways might represent two intriguing treatment options. Treatments directed against HPV are discussed as well. Further evidence is warranted to identify the best treatment modalities for patients with locally advanced, recurrent, and metastatic disease.

InfraRob is a research project funded by the European Commission's research programme Horizon 2020 that aims to maintain integrity, performance, and safety of the road infrastructure through autonomous robotized solutions and modularization. A specific task of the project is focused on the development of a system 3D printer able to extrude a specific mixture for filling in small cracks and potholes, to be integrated with an existing small autonomous carrier. The first step of the research deals with the definition of the optimal parameters of the system 3D printer/mixture, by studying in parallel the material design and the printer design. This paper presents the study performed on a mixture chosen among those commonly used for road potholes repair. The mixture is studied to achieve and balance the different conflicting performances: consistence, flowability homogeneity, and internal structure. In addition to the basic components, the use of special additives has also been explored to improve the plasticity and adhesivity of the mixture. The first phase of tests is conducted to define the main printing controls: i) Extrudability control: materials for 3D printing need to have an acceptable degree of extrudability, which is related to the capacity of a material to pass continuously through the printing head; ii) Flowability control, to ensure the mixture can be easy-pumpable in the delivery system and easy-usable on the crack or the pothole to be filed-in; iii) Setting time control: printing material requires a certain setting time to maintain a consistent flow rate for good extrudability, thus appropriate additives are needed to control the setting time. The second phase includes in situ tests to verify the compaction of the mixture under the traffic loads. The paper presents the results of the lab and in situ tests, and the features of the chosen mix, suitable to be managed by the 3D printer

ABSTRACTThe political and institutional trajectory of Italy was clearly punctuated by the economic upheavals of the pandemic. The articles in the special issue aim to assess the character of the institutional change prompted by the economic response to the pandemic, and in particular by the National Recovery and Resilience Plan (NRRP), in different policy areas. Three contributions analyse the reform dynamics related to the strategic axis of the Italian NRRP, namely digitalization and innovation (Ottone and Barbieri), the ecological transition (Cotta and Domorenok), and social inclusion as concerns labour-market policies (Tassinari). Two contributions focus on two overarching priorities of the NRRP: gender equality (Donà) and development of southern Italy (Cerruto, Cersosimo and Raniolo). Finally, one contribution focuses on reform of the public administration, which has been identified as a key area, affecting horizontally all missions in the NRRP (Di Mascio, Natalini and Profeti). Overall, the articles in the special issue highlight that the pandemic has been followed by a process of institutional change that occurred both incrementally and unevenly, often disguising substantial continuity.

ABSTRACTThe article investigates the impact of the National Recovery and Resilience Plan, complemented by changes in the composition of government at the domestic level, on the patterns of administrative reforms in Italy. We draw on research arguments that rest on historical institutionalism, which constitutes an established approach to the study of administrative reforms. We elaborate on how history has connected well-established patterns of administrative reform to the design and governance of the NRRP measures that aim to provide better public services. We find the strongest support for the research arguments derived from the reactive approach to policy sequencing, entailing the co-existence of pre-pandemic patterns and innovative policy features

One predictor of preterm birth (PTB) is a short cervical length before 24 weeks of gestation. For pregnant women with short cervical length and a history of PTB, cervical cerclage plus progesterone is offered. This procedure has been shown to reduce the risk of PTB, pregnancy loss, and perinatal morbidity and mortality. However, it also increases the risk of preterm, premature rupture of membrane (pPROM). When pPROM occurs, the decision must be made to either remove or retain the cerclage. This decision is a challenge due to a lack of evidence to support retaining cerclage, which could prolong the duration of pregnancy, or removing it, which may decrease the risk chorioamnionitis. In addition, guidelines from international societies are conflicting: a practice bulletin from the American College of Obstetricians and Gynecologists regards both removal and retention of cerclage in pregnancies complicated with pPROM as reasonable options, whereas a practice guideline from the Royal College of Obstetricians and Gynecologists supports the removal of cerclage. The aim of this study was to compare the removal of cervical cerclage with its retention on maternal and perinatal outcomes.This was a systematic review and meta-analysis using an electronic search of Medline, Embase, and Cochrane electronic databases in February 2023. Included were prospective and retrospective publications, reported in English, which evaluated perinatal outcomes of removing or retaining cervical cerclage complicated by pPROM. Excluded were case reports, case series, review articles, letters to the editors, or editorials. The primary outcomes were pregnancy latency from pPROM >48 hours and >7 days. Quality assessment of the included studies used the Newcastle-Ottawa Scale.A total of 6 studies, representing 377 women (169 in the removal group and 208 in the retention group), were included in this systematic review. The removal group had significantly lower rates of pregnancy latency than the retention group at >48 hours (47% vs 85%; odds ratio [OR], 0.15; 95% confidence interval [CI], 0.07–0.31; P< 0.0001) and >7 days (33% vs 57%; OR, 0.30; 95% CI, 0.11–0.83; P= 0.02). However, the removal group also had lower rates than the retention groups of chorioamnionitis (29% vs 41%; OR, 0.57; 95% CI, 0.34–0.96; P= 0.03) and Apgar score <7 at 5 minutes (16% vs 43%; OR, 0.22; 95% CI, 0.08–0.56; P= 0.002). No significant differences were observed in the rates of postpartum endometritis, cesarean delivery, respiratory distress syndrome, neonatal sepsis, intraventricular hemorrhage, necrotizing enterocolitis, birthweight, fetal death, and neonatal mortality.In conclusion, the group that had cervical cerclage removal had a lower risk of experiencing pregnancy latency at >48 hours and >7 days than the group with cerclage retention. However, the retention group had a higher risk of chorioamnionitis and Apgar <7 at 5 minutes.

A major shift occurred in the European Union (EU) approach to tackle the apparently unstoppable rise of populist parties across European countries and to preserve the integrity of the EU polity. EU economic governance seems to have shifted from a logic of conditionality to a logic of solidarity underpinned by a pan-European strategic view allowing EU governance to support and enable public sector reforms at the national level. By investigating the case of Italy as an EU member state, we find that the European governance shift occurring in the wake of the COVID-19 pandemic was largely mediated by the mutating character of Italian populism. A logic of conditionality which was largely centered around EU governance was largely shifted to a logic of solidarity taking into account political conditions in the member countries.

International organizations such as the WHO have worked to raise awareness of the massive infodemic that accompanied the COVID‐19 outbreak and made it hard for people to find trustworthy sources of information and reliable guidance for their decisions. Our contribution focuses on the Italian case, where the Communications Regulatory Authority (AGCOM) was able to act as first mover in its field so as to strategically frame the problem of disinformation in the absence of a pre‐existing policy intervention. An emerging body of research shows that the activity of formally independent regulators is not necessarily limited to the implementation of delegated regulatory competencies. We discuss the implications of the activity of independent regulators for the fight against disinformation during the COVID‐19 pandemic. We find that as a political actor in its own right, the Italian media regulator claimed control over sectoral expertise in order to shape the crucial first steps of the response to the infodemic. Internationale Organisationen wie die WHO haben sich bemüht, das Bewusstsein für die massive «Infodemie» zu schärfen, die den COVID‐19‐Ausbruch begleitete und es den Menschen erschwerte, vertrauenswürdige Informationsquellen und verlässliche Entscheidungshilfen zu finden. Unser Beitrag untersucht den Fall Italiens, wo die Regulierungsbehörde für Kommunikation (AGCOM) als First Mover agieren und das Problem der Desinformation in Ermangelung einer bereits bestehenden politischen Intervention strategisch gestalten konnte. Die neuere Forschung zeigt, dass die Tätigkeit formal unabhängiger Regulierungsbehörden nicht notwendigerweise auf die Umsetzung delegierter Regulierungskompetenzen beschränkt ist. Wir diskutieren in diesem Beitrag die Auswirkungen der Tätigkeit unabhängiger Regulierungsbehörden auf den Kampf gegen Desinformation während der COVID‐19‐Pandemie. Wir stellen zudem fest, dass die italienische Medienregulierungsbehörde die Kontrolle über sektorales Fachwissen beanspruchte und so die entscheidenden ersten Schritte der politischen Antwort auf die Infodemie zu gestalten. Des organisations internationales telles que l'OMS se sont efforcées de faire prendre conscience de l' « infodémie » massive qui a accompagné l'épidémie du COVID‐19 et qui a rendu difficile pour les gens de trouver des sources d'information dignes de confiance et des aides fiables à leurs décisions. Notre contribution se concentre sur le cas de l'Italie, où l'Autorité de régulation des communications (AGCOM) a été en mesure d'agir en tant que premier acteur dans son domaine afin d'encadrer stratégiquement le problème de la désinformation en l'absence d'une intervention politique préexistante. Des recherches récentes montrent que l'activité des régulateurs formellement indépendants ne se limite pas nécessairement à la mise en œuvre des compétences réglementaires déléguées. Nous examinons les implications de l'activité des régulateurs indépendants pour la lutte contre la désinformation pendant la pandémie COVID‐19. Nous constatons que le régulateur italien des médias a revendiqué le contrôle de l'expertise sectorielle afin de façonner les premières étapes cruciales de la réponse à l'infodémie.

(Abstracted from J Matern Fetal Neonatal Med2021;34(21):3614–3622)Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated total bile acids (TBAs) and is the most common liver disease during pregnancy. The etiology and pathophysiology of ICP are not well understood, but genetics, ethnicity, hormones, nutrition, and the environment have been cited as risk factors.

Home-to-school routes are very sensitive areas: they represent, for children, a learning tool for their everyday activities, but if poorly designed, maintained and equipped they can expose them to traffic risks. Sidewalks' inappropriate level of service and poor maintenance, especially, are main factors contributing to walking unsuitability, thus to poor comfort and safety levels for young pedestrians, and more in general for all the vulnerable non-motorized road users. This paper deals with a methodology specifically developed to highlight the quality of the urban environment where the home-to-school routes are located, according to four main criteria: wellbeing, usage, appearance, and safety and security. Each criterion is associated with a checklist including the most relevant features to assess, with a focus on maintenance as a key parameter to create safe and comfortable routes to school. An application, a case study in Rome, where the lack of regular maintenance results into a network of unsafe sidewalks, is also presented, analyzing three different areas where a number of schools are located. Detours when approaching school premises were surveyed, due to the levels of distresses and linked to the poor comfort and safety levels. As the mutual influence of built environment over road safety and maintenance requirements for home-to-school paths is not largely investigated thus far, the paper's goal is to provide advanced knowledge for studies and applications further afield.

Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less.

High-density lipoprotein (HDL) is a diverse group of particles with multiple cardioprotective functions. HDL proteome follows HDL particle complexity. Many proteins were described in HDL, but consistent quantification of HDL protein cargo is still a challenge. To address this issue, the aim of this work was to compare data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methodologies in their abilities to differentiate HDL subclasses through their proteomes. To this end, we first evaluated the analytical performances of DIA and PRM using labeled peptides in pooled digested HDL as a biological matrix. Next, we compared the quantification capabilities of the two methodologies for 24 proteins found in HDL2and HDL3from 19 apparently healthy subjects. DIA and PRM exhibited comparable linearity, accuracy, and precision. Moreover, both methodologies worked equally well, differentiating HDL subclasses’ proteomes with high precision. Our findings may help to understand HDL functional diversity.

Although the construction of block pavements has grown fast in the last decades, there is still a need for simple tools that could be applied to design them. This paper analyzed and verified concrete block pavements for urban and local roads composed of rectangular concrete pavers with plane side surfaces (no interlocking effect). The examined blocks were laid on a bedding sand layer, a cement treated base layer and a granular unbound foundation layer. The commercial finite element (FE) software ANSYS® was used to calculate the response of the pavement when subjected to different loading, construction configurations. Three wheel positions, five blocks patterns, three bedding sand thicknesses and joints gaps have been considered to evaluate stress-strain condition on pavement materials. Fatigue and rutting verification was performed respectively for bound and unbound pavement materials using analytical curves available in the literature. At the end of this study, a proposal for a catalogue is presented. It has nine pavement sets, because it takes into account three values of subgrade capacity (30, 90, and 150 MPa of resilient modulus) and three levels of traffic (400,000, 1,500,000, and 4,000,000 passages of commercial vehicles during the service life). The obtained results provide an inexpensive procedure for the preliminary design of concrete block pavements.

Purpose: The purpose of this paper is to explore the mediation impacts of core, relational and tangible service-quality features on the relationship between customer–frontline employee rapport and customer dependency in an emerging market context. The study examines the moderating effects of relationship age and frequency of customers’ physical visits. Design/methodology/approach: Partial least squares-based structural equation modelling was used to analyse data from a survey of 290 financial services customers in Dhaka, Bangladesh using the convenience sampling technique. Findings: Results show that relational service-quality features had the largest mediation impact on the rapport–dependency relationship, followed by core and tangible service-quality features. Relationship age was not found to be a significant moderator for any relationship. However, the moderation effect of the frequency of customers’ physical visits to the service premises was significant, but only for the link between relational service-quality features and customer dependency and not for the other two types of service-quality features. Research limitations/implications: Data collected from several other emerging markets would provide more rigorous findings: this is recommended as an avenue for further research. Practical implications: Practitioners can manipulate specific relational or tangible service-quality features to increase customer dependency on their firms, thus ensuring longer-term customer retention. Originality/value: This study is the first one to examine the relative significance of the impacts of relational features vs tangible features of services on customer dependency in the emerging market context, with rapport serving as an antecedent.

AbstractThis research contributes to the expanding literature on the determinants of government transparency. It uncovers the dynamics of transparency in the Italian case, which shows an interesting reform trajectory: until the late 1980s no transparency provisions existed; since then, provisions have dramatically increased under the impulse of changing patterns of political competition. The analysis of the Italian case highlights that electoral uncertainty for incumbents is a double-edged sword for institutional reform: on the one hand, it incentivizes the adoption of ever-growing transparency provisions; on the other, it jeopardizes the implementation capacity of public agencies by leading to severe administrative burdens.

A nitrosamine photooxidation reaction is shown to generate a peroxy intermediate by experimental physical-organic methods. The irradiation of phenyl and methyl-substituted nitrosamines in the presence of isotopically labeled 18-oxygen revealed that an O atom was trapped from a peroxy intermediate to trimethylphosphite or triphenylphosphine, or by nitrosamine itself, forming two moles of nitramine. The unstable peroxy intermediate can be trapped at low temperature in postphotolyzed solution in the dark. Chemiluminescence was also observed upon thermal decomposition of the peroxy intermediate, that is, when a postphotolysis low-temperature solution is brought up to room temperature. A DFT study provides tentative information for cyclic nitrogen peroxide species on the reaction surface.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the dysfunction and death of motor neurons through multifactorial mechanisms that remain unclear. ALS has been recognized as a multisystemic disease, and the potential role of skeletal muscle in disease progression has been investigated. Reactive aldehydes formed as secondary lipid peroxidation products in the redox processes react with biomolecules, such as DNA, proteins, and amino acids, resulting in cytotoxic effects. 4-Hydroxy-2-nonenal (HNE) levels are elevated in the spinal cord motor neurons of ALS patients, and HNE-modified proteins have been identified in the spinal cord tissue of an ALS transgenic mice model, suggesting that reactive aldehydes can contribute to motor neuron degeneration in ALS. One biological pathway of aldehyde detoxification involves conjugation with glutathione (GSH) or carnosine (Car). Here, the detection and quantification of Car, GSH, GSSG (glutathione disulfide), and the corresponding adducts with HNE, Car-HNE, and GS-HNE, were performed in muscle and liver tissues of a hSOD1G93AALS rat model by reverse-phase high-performance liquid chromatography coupled to electrospray ion trap tandem mass spectrometry in the selected reaction monitoring mode. A significant increase in the levels of GS-HNE and Car-HNE was observed in the muscle tissue of the end-stage ALS animals. Therefore, analyzing variations in the levels of these adducts in ALS animal tissue is crucial from a toxicological perspective and can contribute to the development of new therapeutic strategies.

Nicotinamide riboside (NR), a NAD+precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD+availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD+increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.

(Abstracted from Ultrasound Obstet Gynecol2021;57:551–559)Cytomegalovirus (CMV) is the most common congenital viral infection that occurs during pregnancy. Prenatal imaging can detect some congenital anomalies associated with CMV, and the presence of a structural anomaly on ultrasound in pregnancies with CMV is associated with a high risk of symptomatic infection and abnormal neurodevelopmental outcomes.