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Abstract Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U34). E4F1-mediated direct transcriptional regulation of Dlat and Elp3, two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensures proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlight a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients.

Estimating the trend of new infections was crucial for monitoring risk and for evaluating strategies and interventions during the COVID-19 pandemic. The pandemic revealed the utility of new data sources and highlighted challenges in interpreting surveillance indicators when changes in disease severity, testing practices or reporting occur. Our study aims to estimate the underlying trend in new COVID-19 infections by combining estimates of growth rates from all available surveillance indicators in Norway. We estimated growth rates by using a negative binomial regression method and aligned the growth rates in time to hospital admissions by maximising correlations. Using a meta-analysis framework, we calculated overall growth rates and reproduction numbers including assessments of the heterogeneity between indicators. We find that the estimated growth rates reached a maximum of 25% per day in March 2020, but afterwards they were between -10% and 10% per day. The correlations between the growth rates estimated from different indicators were between 0.5 and 1.0. Growth rates from indicators based on wastewater, panel and cohort data can give up to 14 days earlier signals of trends compared to hospital admissions, while indicators based on positive lab tests can give signals up to 7 days earlier. Combining estimates of growth rates from multiple surveillance indicators provides a useful description of the COVID-19 pandemic in Norway. This is a powerful technique for a holistic understanding of the trends of new COVID-19 infections and the technique can easily be adapted to new data sources and situations.

Italian olive oil companies play a significant role in this nation's economy, which is among the top in the world for its geomorphological and meteorological characteristics. This research analyzed the performance of three profitability ratios (return on equity (R.O.E.), return on investment (R.O.I.), and return on sales (R.O.S.)) of 3184 companies from 2013 to 2022. Average ratios for each year and critical descriptive statistics were calculated. Broken lines and interpolating curves, obtained from sixth-degree polynomial equations maximizing R2, represent the trends. One-way ANOVA and Tukey-Kramer methods facilitated statistical comparisons between macro-regions. Despite the regular consumption of olive oil, the profitability of businesses has been erratic and fluctuating, probably due to the varying productivity of raw material crops. The pandemic seems to have had no impact. There are no statistically significant differences between macro-areas. The results are helpful to Italian and foreign entrepreneurs who can relate their situation to the average situation in context, highlighting possible gaps that, if negative, must be bridged with a timely management review. National and supranational political authorities can also use this study to orient the frequent support policies in the agricultural and agro-industrial sectors. So too can the bodies in charge of food education, especially for young people, can encourage the use of olive oil where it is lacking. The main limitation of this study was its focus on a small set of profitability ratios. In the future, the study should consider other profitability and asset ratios and investigate investments in sustainability, keeping in mind that all enterprises should contribute to developing eco-friendly production systems.

The paper presents a report that discusses the experience of participation of the authors in the EduHack, an online course designed to train university teachers in the use of digital techniques and learning strategies. This study highlights two issues of great interest in pandemic times. The first one is the structure and the organization of the EduHack course with some suggestions related to its improvement; the second one is Drag&Fly, the project idea of an e-learning web platform developed by the authors during the collaborative part of the course. The experience of participation to EduHack course has been analyzed by authors using concepts and categories of analysis widespread in the pragmatic theoretical tradition, enhancing the possibility of changing the teachers' approach to the design and the implementation of a higher education e-learning course.

Social media has significantly transformed how political discussions and deliberations occur, mainly by providing a digital realm for the public sphere. This study aims to analyse the extent of polarised opinions across Spain, Italy and the United Kingdom regarding COVID-19 during 2020 within social media. To do this, we examined YouTube comments (n=111,808) using automatic analysis and machine-learning techniques based on algorithms. This methodological strategy denoted an innovative and unique quantitative approach for this field of study. In line with previous research, the hypothesis was that the degree of polarization does not crystallize in the same manner in different countries' digital spheres. Therefore, it could be said that higher levels of polarization occur amongst Southern European countries like Spain and Italy (both countries adhering to a polarised pluralism model), compared to other countries ascribing to the liberal model (the United Kingdom in our study), which provides evidence supporting previous research studies. The results confirmed the hypothesis that the polarization of digital deliberation between Spain and Italy is higher than in the United Kingdom. But, also, the findings based on more disaggregated analysis suggest that the most polarized attitudes are even rewarded by other users in Mediterranean countries.

This paper examines some unpublished braziers, currently stored at the National Archaeological Museum of Taranto. Three of them are inscribed with the same anthroponym in the genitive case (Ἑκαταίου), while the remaining eight are anepigraphic. Braziers, which were used both in daily life and as domestic furnishings, were widely distributed throughout the Mediterranean during the Hellenistic period. These new findings further confirm the involvement of Taranto, along with some other Italian cities, in the trade and circulation of these objects throughout the Mediterranean area. This paper aims to provide an overview of this phenomenon, with a particular focus on the identity of Hekataios and the characteristics of his production.

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells’ ROS rapidly increased and progressively diminished over time, in breast cancer, cells’ ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.

Detailed studies of the equiprobable auditory Go/NoGo task have allowed for the development of a sequential-processing model of the perceptual and cognitive processes involved. These processes are reflected in various components differentiating the Go and NoGo event-related potentials (ERPs). It has long been established that electroencephalography (EEG) changes through normal lifespan development. It is also known that ERPs and behaviour in the equiprobable auditory Go/NoGo task change from children to young adults, and again in older adults. Here, we provide a novel examination of links between in-task prestimulus EEG, poststimulus ERPs, and behaviour in three gender-matched groups: children (8–12 years), young adults (18–24 years), and older adults (59–74 years). We used a frequency Principal Component Analysis (f-PCA) to estimate prestimulus EEG components and a temporal Principal Component Analysis (t-PCA) to separately estimate poststimulus ERP Go and NoGo components in each age group to avoid misallocation of variance. The links between EEG components, ERP components, and behavioural measures differed markedly between the groups. The young adults performed best and accomplished this with the simplest EEG–ERP–behaviour brain dynamics pattern. The children performed worst, and this was reflected in the most complex brain dynamics pattern. The older adults showed some reduction in performance, reflected in an EEG–ERP–behaviour pattern with intermediate complexity between those of the children and young adults. These novel brain dynamics patterns hold promise for future developmental research.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

The paper discusses the first edition of a list of personal names inscribed on a terracotta tile. The document, which dates back to the early Hellenistic period, was brought to light in 1988 from a craft area site in Taranto (via Leonida 52). The type of inscription seems to refer to the genre of defixiones written in the form of a nominal list, while the type of medium appears to be rather unusual for a magical text. Comparison with a coeval defixio from Taranto and similar documents shows that magic lists are known to have been used in Taranto during the Hellenistic period, as well as in other areas of Magna Graecia and Sicily.

Abstract INTRODUCTION This study primarily aimed to evaluate the efficacy and safety of SaiLuoTong (SLT) on cognition in mild cognitive impairment (MCI). METHODS Community‐dwelling people with MCI aged ≥60 years were randomly assigned to 180 mg/day SLT or placebo for 12 weeks. RESULTS Thirty‐nine participants were randomized to each group (N = 78); 65 were included in the final analysis. After 12 weeks, the between‐groups difference in Logical Memory delayed recall scores was 1.40 (95% confidence interval [CI]: 0.22 to 2.58; P = 0.010); Delis–Kaplan Executive Function System Trail Making Test Condition 4 switching and contrast scaled scores were 1.42 (95% CI: –0.15 to 2.99; P = 0.038) and 1.56 (95% CI: –0.09 to 3.20; P = 0.032), respectively; Rey Auditory Verbal Learning Test delayed recall was 1.37 (95% CI: –0.10 to 2.84; P = 0.034); and Functional Activities Questionnaire was 1.21 (95% CI: –0.21 to 2.63; P = 0.047; P < 0.001 after controlling for baseline scores). DISCUSSION SLT is well tolerated and may be useful in supporting aspects of memory retrieval and executive function in people with MCI. Highlights SaiLuoTong (SLT) improves delayed memory retrieval and executive function in people with mild cognitive impairment (MCI). SLT is well tolerated in people ≥ 60 years. The sample of community dwellers with MCI was well characterized and homogeneous.

In this study the authors investigate household transmission of SARS-CoV-2 in Norway. They find that the secondary attack rate was higher for Omicron than Delta, but that among three-dose vaccinated contacts the secondary attack rate was lower for both variants compared to contacts with two doses.

Promoting the use of public transport is increasingly urgent in our society, both to reduce traffic congestion, air pollution and stress levels, and to ensure the high level of mobility demanded by citizens. The lack of continuous on-trip assistance for public transport users discourages many travellers. Thus, the main objective of this work is to design a personal digital travel companion for outdoor location and event detection based on Bluetooth Low Energy, which can be used for intelligent transport technology. After analysing the functional requirements, the proposal is implemented as a mobile application for beacon-based event detection. The system includes an algorithm aided by fuzzy logic to determine the action to be carried out by the user at all times, being able to distinguish between different possible events when more than one beacon is detected. To defend the scheme against possible attacks based on beacon forgery or user tracking, the proposal includes different forms of authentication for data sent from beacons and data sent from the mobile application. The results obtained in simulations show that the proposed system is a viable guidance solution for public transport, including energy saving as one of its main advantages.

IntroductionOdors are closely linked to emotions, play an important role in the well-being of individuals and can influence mood. Despite these crucial properties, the hedonic responses to odors of people with profound intellectual and multiple disabilities (PIMD) remain little explored.AimThis within-subjects study aims to examine whether children and young people with PIMD react in a differentiated way to odors evaluated as pleasant or unpleasant by neurotypical adults and, if so, with which behaviors. The influence of their global mood on their emotional responses to odors is also examined.MethodTwenty children and young people (7–18 years old) with PIMD were exposed to four pairs of hedonically contrasted odors. A control stimulus was presented before each odorant. Five emotional responses, one physiological reaction (nausea reactions), and three responses reflecting approach toward or avoidance of the stimulus were recorded throughout the duration of the stimulus exposure. The participants’ global mood status was measured before the start of the research with the French version of the Mood, Interest and Pleasure Questionnaire (Ross and Oliver, 2003).ResultsThe results show that when exposed to pleasant odorants, participants kept their heads aligned with the odorant source longer, smiled longer, and produced more positive vocalizations. In contrast, unpleasant odorants elicit more pouts and grimaces. Nausea reactions occurred in the presence of unpleasant odorants. The hedonic responses were more marked during the second presentation of the stimuli. Participants with a higher MIPQ score showed significantly more emotional reactions to odors.ConclusionThe results confirm the presence of olfactory preferences in participants with PIMD and the existence of a link between their mood, emotions and olfactory hedonic processing. They prompt the use of odors to support not only the cognitive development of this population, but also their mood and their emotional regulation abilities.

Estimating the trend of new infections was crucial for monitoring risk and for evaluating strategies and interventions during the COVID-19 pandemic. The pandemic revealed the utility of new data sources and highlighted challenges in interpreting surveillance indicators when changes in disease severity, testing practices or reporting occur. Our study aims to estimate the underlying trend in new COVID-19 infections by combining estimates of growth rates from all available surveillance indicators in Norway. We estimated growth rates by using a negative binomial regression method and aligned the growth rates in time to hospital admissions by maximising correlations. Using a meta-analysis framework, we calculated overall growth rates and reproduction numbers including assessments of the heterogeneity between indicators. We find that the estimated growth rates reached a maximum of 25% per day in March 2020, but afterwards they were between -10% and 10% per day. The correlations between the growth rates estimated from different indicators were between 0.5 and 1.0. Growth rates from indicators based on wastewater, panel and cohort data can give up to 14 days earlier signals of trends compared to hospital admissions, while indicators based on positive lab tests can give signals up to 7 days earlier. Combining estimates of growth rates from multiple surveillance indicators provides a useful description of the COVID-19 pandemic in Norway. This is a powerful technique for a holistic understanding of the trends of new COVID-19 infections and the technique can easily be adapted to new data sources and situations. [ABSTRACT FROM AUTHOR]

Abstract Background Regression models are often used to explain the relative risk of infectious diseases among groups. For example, overrepresentation of immigrants among COVID-19 cases has been found in multiple countries. Several studies apply regression models to investigate whether different risk factors can explain this overrepresentation among immigrants without considering dependence between the cases. Methods We study the appropriateness of traditional statistical regression methods for identifying risk factors for infectious diseases, by a simulation study. We model infectious disease spread by a simple, population-structured version of an SIR (susceptible-infected-recovered)-model, which is one of the most famous and well-established models for infectious disease spread. The population is thus divided into different sub-groups. We vary the contact structure between the sub-groups of the population. We analyse the relation between individual-level risk of infection and group-level relative risk. We analyse whether Poisson regression estimators can capture the true, underlying parameters of transmission. We assess both the quantitative and qualitative accuracy of the estimated regression coefficients. Results We illustrate that there is no clear relationship between differences in individual characteristics and group-level overrepresentation —small differences on the individual level can result in arbitrarily high overrepresentation. We demonstrate that individual risk of infection cannot be properly defined without simultaneous specification of the infection level of the population. We argue that the estimated regression coefficients are not interpretable and show that it is not possible to adjust for other variables by standard regression methods. Finally, we illustrate that regression models can result in the significance of variables unrelated to infection risk in the constructed simulation example (e.g. ethnicity), particularly when a large proportion of contacts is within the same group. Conclusions Traditional regression models which are valid for modelling risk between groups for non-communicable diseases are not valid for infectious diseases. By applying such methods to identify risk factors of infectious diseases, one risks ending up with wrong conclusions. Output from such analyses should therefore be treated with great caution.

Growth and maturation of the fetal gastrointestinal tract near term prepares the offspring for the onset of enteral nutrition at birth. Structural and functional changes are regulated by the prepartum rise in cortisol in the fetal circulation, although the role of the coincident rise in plasma tri-iodothyronine (T3) is unknown. This study examined the effect of hypothyroidism on the structural development of the gastrointestinal tract and the activity of brush-border digestive enzymes in the ovine fetus near term. In intact fetuses studied between 100 and 144 days of gestation (dGA; term ∼145 days), plasma concentrations of T3, cortisol and gastrin; the mucosal thickness in the abomasum, duodenum, jejunum and ileum; and intestinal villus height and crypt depth increased with gestational age. Removal of the fetal thyroid gland at 105–110 dGA suppressed plasma thyroxine (T4) and T3 concentrations to the limit of assay detection in fetuses studied at 130 and 144 dGA, and decreased plasma cortisol and gastrin near term, compared to age-matched intact fetuses. Hypothyroidism was associated with reductions in the relative weights of the stomach compartments and small intestines, the outer perimeter of the intestines, the thickness of the gastric and intestinal mucosa, villus height and width, and crypt depth. The thickness of the mucosal epithelial cell layer and muscularis propria in the small intestines were not affected by gestational age or treatment. Activities of the brush border enzymes varied with gestational age in a manner that depended on the enzyme and region of the small intestines studied. In the ileum, maltase and dipeptidyl peptidase IV (DPPIV) activities were lower, and aminopeptidase N (ApN) were higher, in the hypothyroid compared to intact fetuses near term. These findings highlight the importance of thyroid hormones in the structural and functional development of the gastrointestinal tract near term, and indicate how hypothyroidism in utero may impair the transition to enteral nutrition and increase the risk of gastrointestinal disorders in the neonate.

The COVID-19 pandemic has had very negative effects on public transport systems. These effects have compromised the role they should play as enablers of social equity and environmentally sustainable mobility and have caused serious economic losses for public transport operators. For this reason, in the context of pandemics, meaningful epidemiological information gathered in the specific framework of these systems is of great interest. This article presents the findings of an investigation into the risk of transmission of a respiratory infectious disease in an intercity road transport system that carries millions of passengers annually. To achieve this objective, a data mining methodology was used to generate the data required to ascertain the level of risk. Using this methodology, the occupancy of vehicle seats by passengers was simulated using two different strategies. The first is an empirical approach to the behaviour of passengers when occupying a free seat and the second attempts to minimise the risk of contagion. For each of these strategies, the interactions with risk of infection between passengers were estimated, the patterns of these interactions on the different routes of the transport system were obtained using k-means clustering technique, and the impact of the strategies was analysed.

The p53 tumor suppressor is also a regulator of metabolism, but the mechanisms controlling p53-associated metabolic activities remain poorly understood. Here the authors report that the deletion of the multifunctional protein E4F1 is protective against diet-induced obesity in mice, and E4F1 regulates adipocyte lipid metabolism through p53.

Coronary bifurcation lesion (CBL) is a common but challenging scenario in percutaneous coronary interventions. Drug-coated balloons (DCBs) are modern devices with attractive perspective in CBL treatment. In-stent restenosis, small vessel and diffuse de-novo coronary artery disease have been, so far, considered the ideal scenario for DCBs application. Studies assessing DCBs in de-novo CBL demonstrated the safety and efficacy of this strategy. However, the heterogeneity of the study populations and the presence of methodological limitations prevent from drawing definite recommendations. Considering that the best treatment of bifurcations has not yet been defined, the “leaving nothing behind” philosophy will be the topic of future studies.

The COVID-19 pandemic is challenging nations with devastating health and economic consequences. The spread of the disease has revealed major geographical heterogeneity because of regionally varying individual behaviour and mobility patterns, unequal meteorological conditions, diverse viral variants, and locally implemented non-pharmaceutical interventions and vaccination roll-out. To support national and regional authorities in surveilling and controlling the pandemic in real-time as it unfolds, we here develop a new regional mathematical and statistical model. The model, which has been in use in Norway during the first two years of the pandemic, is informed by real-time mobility estimates from mobile phone data and laboratory-confirmed case and hospitalisation incidence. To estimate regional and time-varying transmissibility, case detection probabilities, and missed imported cases, we developed a novel sequential Approximate Bayesian Computation method allowing inference in useful time, despite the high parametric dimension. We test our approach on Norway and find that three-week-ahead predictions are precise and well-calibrated, enabling policy-relevant situational awareness at a local scale. By comparing the reproduction numbers before and after lockdowns, we identify spatially heterogeneous patterns in their effect on the transmissibility, with a stronger effect in the most populated regions compared to the national reduction estimated to be 85% (95% CI 78%-89%). Our approach is the first regional changepoint stochastic metapopulation model capable of real time spatially refined surveillance and forecasting during emergencies.

Non-pharmaceutical interventions, including promotion of social distancing, have been applied extensively in managing the COVID-19 pandemic. Understanding cognitive and psychological factors regulating precautionary behavior is important for future management. The present study examines the importance of selected factors as predictors of having visited or intended to visit crowded places. Six online questionnaire-based waves of data collection were conducted in April–October 2020 in a Norwegian panel (≥18 years). Sample size at Wave 1 was 1,400. In the present study, “Visited or intended to visit crowded places” for different types of locations were the dependent variables. Predictors included the following categories of items: Perceived response effectiveness, Self-efficacy, Vulnerability, Facilitating factors and Barriers. Data were analyzed with frequency and percentage distributions, descriptives, correlations, principal components analysis, negative binomial-, binary logistic-, and multiple linear regression, and cross-lagged panel models. Analyses of dimensionality revealed that a distinction had to be made between Grocery stores, a location visited by most, and locations visited by few (e.g., “Pub,” “Restaurants,” “Sports event”). We merged the latter set of variables into a countscore denoted as “Crowded places.” On the predictor side, 25 items were reduced to eight meanscores. Analyses of data from Wave 1 revealed a rather strong prediction of “Crowded places” and weaker associations with “Supermarket or other store for food.” Across waves, in multiple negative binomial regression models, three meanscore predictors turned out to be consistently associated with “Crowded places.” These include “Response effectiveness of individual action,” “Self-efficacy with regard to avoiding people,” and “Barriers.” In a prospective cross-lagged model, a combined Response effectiveness and Self-efficacy score (Cognition) predicted behavior (“Visited or intended to visit crowded places”) prospectively and vice versa. The results of this study suggest some potential to reduce people's visits to crowded locations during the pandemic through health education and behavior change approaches that focus on strengthening individuals' perceived response effectiveness and self-efficacy.

Origanum vulgare L. is an aromatic plant that exerts antibacterial, antioxidant, anti-inflammatory, and antitumor activities, mainly due to its essential oil (EO) content. In this study, we investigated the possible mechanism underlying the in vitro antitumor activity of EO extracted by hydrodistillation of dried flowers and leaves of Origanum vulgare L. grown in Sicily (Italy) in MDA-MB-231 and MCF-7 breast cancer cell lines. Gas chromatography–mass spectrometry analysis of Oregano essential oil (OEO) composition highlighted the presence of twenty-six major phytocompounds, such as p-cymene, γ-terpinene, and thymoquinone p-acetanisole. OEO possesses strong antioxidant capacity, as demonstrated by the DPPH test. Our studies provided evidence that OEO reduces the viability of both MCF-7 and MDA-MB-231 cells. The cytotoxic effect of OEO on breast cancer cells was partially counteracted by the addition of z-VAD-fmk, a general caspase inhibitor. Caspases and mitochondrial dysfunction appeared to be involved in the OEO-induced death mechanism. Western blotting analysis showed that OEO-induced activation of pro-caspases-9 and -3 and fragmentation of PARP decreased the levels of Bcl-2 and Bcl-xL while increasing those of Bax and VDAC. In addition, fluorescence microscopy and cytofluorimetric analysis showed that OEO induces a loss of mitochondrial membrane potential in both cell lines. Furthermore, we tested the effects of p-cymene, γ-terpinene, thymoquinone, and p-acetanisole, which are the main components of OEO. Our findings highlighted that the effect of OEO on MDA-MB-231 and MCF-7 cells appears to be mainly due to the combination of different constituents of OEO, providing evidence of the potential use of OEO for breast cancer treatment.

Introduction: Achalasia following bariatric surgery is a rare phenomenon with diverse potential physiopathological origins. Aims: This article aims to explore the hypothetical physiopathological connection between bariatric surgery and the subsequent onset of achalasia. Material and Methods: A review was conducted to identify studies reporting cases of peroral endoscopic myotomy (POEM) after bariatric procedures and detailing the outcomes in terms of the technical and clinical success. Additionally, a case of a successful POEM performed on a patient two years after undergoing laparoscopic sleeve gastrectomy (LSG) is presented. Results: The selection criteria yielded eight studies encompassing 40 patients treated with POEM for achalasia after bariatric surgery: 34 after Roux-en-Y gastric bypass (RYGB) and 6 after LSG. The studies reported an overall technical success rate of 97.5%, with clinical success achieved in 85% of cases. Adverse events were minimal, with only one case of esophageal leak treated endoscopically. However, a postprocedural symptomatic evaluation was notably lacking in most of the included studies. Conclusions: Achalasia poses a considerable challenge within the bariatric surgery population. POEM has emerged as a technically viable and safe intervention for this patient demographic, providing an effective treatment option where surgical alternatives for achalasia are limited. Our findings highlight the promising outcomes of POEM in these patients, but the existing data remain limited. Hence, prospective studies are needed to elucidate the optimal pre-surgical assessment and timing of endoscopic procedures for optimizing outcomes.

Abstract SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.

Marco Cascella,1 Alfredo Del Gaudio,2 Alessandro Vittori,3 Sabrina Bimonte,1 Paola Del Prete,4 Cira Antonietta Forte,1 Arturo Cuomo,1 Elvio De Blasio2,5 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, Italy; 2DSC Anestesia e Rianimazione 2, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, 71013, FG, Italy; 3Department of Anesthesiology and Critical Care, ARCO, Bambino Gesù Children’s Hospital, Rome, Italy; 4Direzione Scientifica, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, Italy; 5Multidisciplinary Emergency Unit for COVID-19 Campania, Naples, 80100, ItalyCorrespondence: Sabrina BimonteDivision of Anesthesia and Pain Medicine, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, ItalyTel +39 0815903221Email s.bimonte@istitutotumori.na.itAbstract: Although the respiratory manifestations of COVID-19 are predominant, signs and symptoms of an extra-pulmonary involvement are usually encompassed among the clinical picture of the disease. Several painful manifestations can occur during the acute phase but also as short- or long-term complications. Myalgia, joint pain, sore throat, abdominal pain, chest pain, and headache usually accompany respiratory symptoms, but they can also occur as isolated clinical findings or can be expressed regardless of the severity of COVID-19. On these premises, given the vast spectrum of clinical manifestations and the complexity of their pathogenesis, it would be more appropriate to refer to “COVID-pain”, an umbrella term useful for encompassing all these clinical manifestations in a separate chapter of the disease. In this scenario, we addressed the topic from a molecular perspective, trying to provide explanations for the underlying pathophysiological processes. Consequently, this narrative review is aimed at dissecting the mechanisms of acute and chronic painful manifestations, summarizing fundamental concepts on the matter, controversies, current research gaps, and potential developments in this field.Keywords: COVID-19, SARS-CoV-2, COVID-pain, COVID-19 complications

Abstract Samples used in biomedical research are often collected over years, in some cases from subjects that may have died and thus cannot be retrieved in any way. The value of these samples is priceless. Sample misidentification or mix-up are unfortunately common problems in biomedical research and can eventually result in the publication of incorrect data. Here we have compared the Fluidigm SNPtrace and the Agena iPLEX Sample ID panels for the authentication of human genomic DNA samples. We have tested 14 pure samples and simulated their cross-contamination at different percentages (2%, 5%, 10%, 25% and 50%). For both panels, we report call rate, allele intensity/probability score, performance in distinguishing pure samples and contaminated samples at different percentages, and sex typing. We show that both panels are reliable and efficient methods for sample authentication and we highlight their advantages and disadvantages. We believe that the data provided here is useful for sample authentication especially in biorepositories and core facility settings.

Abstract Background Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac cellular landscape in murine diabetes to identify potential cellular protagonists in the diabetic heart. Methods Diabetes was induced in male FVB/N mice by low-dose streptozotocin and a high-fat diet for 26-weeks. Cardiac function was measured by echocardiography at endpoint. Flow cytometry was performed on cardiac ventricles as well as blood, spleen, and bone-marrow at endpoint from non-diabetic and diabetic mice. To validate flow cytometry results, immunofluorescence staining was conducted on left-ventricles of age-matched mice. Results Mice with diabetes exhibited hyperglycaemia and impaired glucose tolerance at endpoint. Echocardiography revealed reduced E:A and e’:a’ ratios in diabetic mice indicating diastolic dysfunction. Systolic function was not different between the experimental groups. Detailed examination of cardiac cellularity found resident mesenchymal cells (RMCs) were elevated as a result of diabetes, due to a marked increase in cardiac fibroblasts, while smooth muscle cells were reduced in proportion. Moreover, we found increased levels of Ly6Chi monocytes in both the heart and in the blood. Consistent with this, the proportion of bone-marrow haematopoietic stem cells were increased in diabetic mice. Conclusions Murine diabetes results in distinct changes in cardiac cellularity. These changes—in particular increased levels of fibroblasts—offer a framework for understanding how cardiac cellularity changes in diabetes. The results also point to new cellular mechanisms in this context, which may further aid in development of pharmacotherapies to allay the progression of cardiomyopathy associated with diabetes.