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Marinella Paciello,1 Giulia Ballarotto,2 Luca Cerniglia,1 Pietro Muratori3 1Faculty of Psychology, Uninettuno Telematic International University, Rome, Italy; 2Department of Dynamic and Clinical Psychology, “Sapienza” University, Rome, Italy; 3IRCCS Fondazione Stella Maris, Scientific, Institute of Child Neurology and Psychiatry, Calambrone, Pisa, ItalyCorrespondence: Marinella PacielloFaculty of Psychology, Uninettuno Telematic International University, Corso Vittorio Emanule II, Rome 39 00186, ItalyEmail m.paciello@uninettunouniversity.netAbstract: Disruptive behavior could represent an (un)moral behavioral component of multi-dimensional construct of morality that includes affective and cognitive aspects. Thus, it is pivotal to investigate their interplay between affective and cognitive processes the better to understand how to intervene to contrast disruptive behavior and its antisocial outcomes. The present review has examined the relationship between affective and cognitive processes implied in moral functioning by focusing on callous-unemotional traits (CU) and moral disengagement. Starting from 1005 records identified by PsycINFO, Pubmed, and Pubpsych, only 13 studies have been selected. These studies show different theoretical approaches and methodologies and put in evidence the nuances of possible interactions of CU and moral disengagement during adolescence based on different research field. Overall, most of the scholars seem to conclude that different interplay can be plausible, suggesting that it is likely that during the adolescence the influence of moral disengagement and CU is reciprocal and longitudinal. Specifically, in adolescents with Disruptive Behavior Disorders CU and moral disengagement can move together in organizing and becoming chronic of antisocial affective-cognitive system, and in particular moral disengagement may give a free way to engage in disruptive behavior.Keywords: disruptive behavior, callous-unemotional traits, moral disengagement, adolescence, morality

Gabriele Masi,1 Simone Pisano,2 Paola Brovedani,1 Gioia Maccaferri,1 Azzurra Manfredi,1 Annarita Milone,1 Annalaura Nocentini,3 Lisa Polidori,1 Laura Ruglioni,1 Pietro Muratori1 1IRCCS Fondazione Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Italy; 2Clinic of Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; 3Department of Sciences of Education and Psychology, University of Florence, Florence, Italy Purpose: Our aims were to explore the developmental trajectories of callous–unemotional (CU) traits using a growth curve analysis in Italian children with disruptive behavior disorders treated with a multimodal intervention, and to test both predictors and distal outcomes of CU traits trajectories. Patients and method: One hundred and sixty-eight children were enrolled, of whom 24 were lost in the follow-up and 144 were followed up from ages 8–9 to 14–15 years with four assessment points. Patients included 128 males (88.9%) with a mean age of 8.7 years, 96 with oppositional defiant disorder (66.7%) and 48 with conduct disorder (CD) (33.3%). The developmental trajectories of CU traits were assessed with the Inventory of Callous–Unemotional Traits (ICU). Results: Our findings revealed that CU features were likely to fit a quadratic model from childhood to adolescence. The CU traits tended to decrease during childhood, with stabilization in adolescence and a significant variability in the growth curves. Pretreatment CD and higher levels of externalizing behavioral problems were associated with higher level of CU traits at baseline, whereas positive parenting was associated with lower levels. No significant effects were found for all the other predictors (socioeconomic status, negative parenting, combined pharmacotherapy). Regarding outcomes into adolescence, both higher levels of CU traits at the baseline and a lower decrease of CU traits across time points predicted a higher risk of CD diagnosis, and higher rate of referrals to mental health services and of substance use. Furthermore, pretreatment CD and negative parenting predicted a higher risk of substance use into adolescence. Conclusion: Our findings suggest that a close monitoring of CU traits in referred children with disruptive behavior disorders may help to detect the patients at higher risk of poor outcome. Keywords: conduct disorder, oppositional defiant disorder, callous–unemotional traits, aggressive behavior, child psychiatry, psychopathy

Abstract Background Despite their apparent dissimilarity, Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD) share many features, especially in terms of social and emotional difficulties. In recent years, empathic abilities in AN have been frequently assessed using self-report measures. Otherwise, the director task (DT) has been used to investigate the ability to take the visual perspective of another individual in a communicative context, using eye-tracking technology. The aim of the current study was to test the presence of autism-relevant features in AN, through: (i) comparing self-reported autistic traits and empathic abilities in a group of young inpatients with AN and age/gender matched healthy controls (HC); (ii) comparing performance on the director paradigm. Methods The participants were females in the age-range between 11 and 18 years: 24 with AN and 23 HC. Autistic traits, empathic abilities, and severity of the eating disorder were respectively measured using: the Autism Quotient (AQ), the Interpersonal Reactivity Index (IRI), and the Eating Disorder Inventory-3 (EDI-3). Both groups performed a computerized task in which a director instructed them to move objects placed on a set of shelves using a mouse, while their eye gaze was tracked. A total of 36 shelf configurations, divided into three categories (with dimensional distractor – with spatial distractor – control), were created. Results Subjects with AN showed higher autistic traits than HC. Eye-tracking data revealed that subjects with AN took longer to decide which object to select and where to move it, both in distractor-trials and in control-trials. In the AN group, we found a significant negative correlation between the total score of the AQ and the number of fixations to the irrelevant object in the dimensional control condition -in which the subjects were asked to focus on dimensional aspects of the object (large-small)-. Conclusions Autistic traits were over-represented in a group of young inpatients with AN. Through the use of eye-tracking technology, this exploratory study documented some differences between AN inpatients and HC in their online processes during the perspective taking tasks, which could be considered a target of tailored intervention. A larger sample of patients is needed to confirm these preliminary findings.

Abstract Background Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients’ reported symptomatology is still unclear. Methods Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. Results We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102–123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. Conclusions In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Previous studies suggest that autism spectrum disorders are characterized by alterations in the microbiota-gut-brain axis. Probiotics may modify the composition and the functionality of the gut microbiota of autism spectrum disorder individuals, with possible cascading effects on brain function. In this study, we analyzed possible brain modifications induced by the administration of probiotics in 46 children with autism spectrum disorder using electroencephalography. A randomized 6-month controlled trial was performed. In subjects treated with probiotics, we observed a decrease of power in frontopolar regions in beta and gamma bands, and increased coherence in the same bands together with a shift in frontal asymmetry, which suggests a modification toward a typical brain activity. Electroencephalography measures were significantly correlated with clinical and biochemical measures. These findings support the importance of further investigations on probiotics' benefits in autism spectrum disorder to better elucidate mechanistic links between probiotics supplementation and changes in brain activity.

Satisfaction with the detection process of autism and its determinants was investigated using data from the Autism Spectrum Disorder in the European Union (2015-2018) network. A total of 1342 family members, including 1278 parents, completed an online survey collecting information about their experience and satisfaction with the early detection of autism in their child. Overall, the level of satisfaction varied considerably from one respondent to another. Difficulty in finding information about detection services, lack of professional guidance and support in response to first concerns, finding a diagnostic service on one's own, and a delay of more than 4 months between the confirmation of concerns and the first appointment with a specialist were all experiences individually associated with greater odds of being less satisfied. Using a dominance analysis approach, we further identified professional guidance and support in response to first concerns as the most important predictor of the level of satisfaction. These findings highlight the aspects of the process that need to be improved to enhance the experience of the detection process and are therefore relevant to guide health administrations toward actions to be implemented to this effect.

Background: People with intellectual disability often receive diagnoses which may complicate their clinical care. Among these, personality disorder diagnoses are still considered contentious. Little is also known on the perspectives of staff caring for people with intellectual disability who have received a personality disorder diagnosis. Methods: Three focus groups were carried out to explore 15 healthcare professionals' subjective experiences of working with people with intellectual disability who also have a recorded additional diagnosis of personality disorder. Data were analysed through thematic analysis. Findings: Four overarching themes were identified: (a) diagnostic issues and the need for person-centred approaches; (b) challenges and adjustments to working with combined intellectual disability and PD diagnoses; (c) the importance of multidisciplinary team training, support, and cohesion; (d) provision issues and barriers to service access. Conclusions: The themes are outlined in depth and a number of implications for clinical management and service improvement are discussed.

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus.

Summary: Climate change has prompted many communities to set targets for carbon-free power supplies, but they often lack data-driven strategies to achieve them. We present a comprehensive analysis of an entirely renewable electric power system that can maintain operating reliability and resource adequacy using detailed models of the city of Los Angeles power grid. In consultation with the operating utility, the Los Angeles Department of Water and Power (LADWP), and the local community, we develop four supply scenarios across three demand projections to analyze which types of infrastructure and operational changes would achieve reliable electricity at least cost. We find that a reliable, 100%-renewable power system yielding more than $1 billion annually in health and climate co-benefits is achievable. Solar can supply most future energy needs, while combustion turbines that use renewable, storable carbon-neutral fuels are key to maintaining reliability. This study provides a replicable methodology that other jurisdictions globally can follow. Science for society: Communities and businesses nationwide have set ambitious goals to combat climate change by generating 100% of their electricity from carbon-free or renewable energy sources. Until now, there has been no comprehensive analysis of the possible pathways to achieve these goals on the scale needed to power the largest US cities. Here, we present findings from the Los Angeles 100% Renewable Energy Study (LA100), a thorough and wide-reaching assessment of the factors needed to make a fully renewable utility system operate reliably and deliver adequate electricity to more than 4 million residents. Our analysis uses detailed models of the city’s power grid to examine not just renewable resource options and technical solutions related to generation, transmission, and distribution systems but also the balance of supply and demand, variability and reliability, and affordability and viability—all through the lens of changing demographics and climate conditions.

Abstract Objectives Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well‐appearing febrile pediatric patients presenting to the emergency department (ED). Methods This is a cross‐sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92–2.12). Conclusions Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well‐appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well‐appearing pediatric patients presenting to the ED.

Summary: Medium- and heavy-duty vehicles are 21% of US transportation greenhouse gas (GHG) emissions and a major source of air pollution. We explore how the total cost of driving (TCD) of zero-emission vehicles (ZEVs), including battery electric vehicles and hydrogen fuel cell electric vehicles (EVs and FCEVs), could evolve under alternative scenarios. With continued improvements in vehicles and fuels, ZEVs can rapidly become viable, potentially reaching TCD parity or better compared to diesel vehicles by 2035 for all market segments. For heavy long-haul trucks, EVs become competitive on a TCD basis at charging costs below $0.18/kWh, while FCEVs become competitive on a TCD basis at hydrogen costs below $5/kg. A full transition to ZEV sales by 2035 results in 65% emissions reductions by 2050 compared to 2019 without supportive policies. Incentives such as the Inflation Reduction Act vehicle purchase credits further accelerate ZEV TCD competitiveness with major adoption opportunities over the next five years.

IntroductionPeripheral nerves are frequently affected by lesions caused by traumatic or iatrogenic damages, resulting in loss of motor and sensory function, crucial in orthopedic outcomes and with a significant impact on patients’ quality of life. Many strategies have been proposed over years to repair nerve injuries with substance loss, to achieve musculoskeletal reinnervation and functional recovery. Allograft have been tested as an alternative to the gold standard, the autograft technique, but nerves from donors frequently cause immunogenic response. For this reason, several studies are focusing to find the best way to decellularize nerves preserving either the extracellular matrix, either the basal lamina, as the key elements used by Schwann cells and axons during the regenerative process.MethodsThis study focuses on a novel decellularization protocol for porcine nerves, aimed at reducing immunogenicity while preserving essential elements like the extracellular matrix and basal lamina, vital for nerve regeneration. To investigate the efficacy of the decellularization protocol to remove immunogenic cellular components of the nerve tissue and to preserve the basal lamina and extracellular matrix, morphological analysis was performed through Masson’s Trichrome staining, immunofluorescence, high resolution light microscopy and transmission electron microscopy. Decellularized porcine nerve graft were then employed in vivo to repair a rat median nerve lesion. Morphological analysis was also used to study the ability of the porcine decellularized graft to support the nerve regeneration.Results and DiscussionThe decellularization method was effective in preparing porcine superficial peroneal nerves for grafting as evidenced by the removal of immunogenic components and preservation of the ECM. Morphological analysis demonstrated that four weeks after injury, regenerating fibers colonized the graft suggesting a promising use to repair severe nerve lesions. The idea of using a porcine nerve graft arises from a translational perspective. This approach offers a promising direction in the orthopedic field for nerve repair, especially in severe cases where conventional methods are limited.

Abstract Passenger and freight travel account for 28% of U.S. greenhouse gas (GHG) emissions today. We explore pathways to reduce transportation emissions using NREL’s TEMPO model under bounding assumptions on future travel behavior, technology advancement, and policies. Results show diverse routes to 80% or more well-to-wheel GHG reductions by 2050. Rapid adoption of zero-emission vehicles coupled with a clean electric grid is essential for deep decarbonization; in the median scenario, zero-emission vehicle sales reach 89% for passenger light-duty and 69% for freight trucks by 2030 and 100% sales for both by 2040. Up to 3,000 terawatt-hours of electricity could be needed in 2050 to power plug-in electric vehicles. Increased sustainable biofuel usage is also essential for decarbonizing aviation (10–42 billion gallons needed in 2050) and to support legacy vehicles during the transition. Managing travel demand growth can ease this transition by reducing the need for clean electricity and sustainable fuels.

Background: Patent foramen ovale (PFO) is often diagnosed in patients with cryptogenic stroke, aged > 60–65 years, but few data report the outcomes of PFO closure in elderly patients. Methods: Consecutive patients undergoing PFO closure at a single institution between January 2006 and December 2011 were included. Baseline clinical features and cerebral imaging data were collected, and a RoPE score was calculated for each patient. Procedural data were recorded as well as medical therapy upon discharge. All-cause death, ischemic stroke, TIA and systemic embolism recurrence at long-term follow-up were investigated, as well as new atrial fibrillation onset. Results: Overall, 462 patients were included, of whom 64 (13.8%) were aged ≥ 65 years. Female gender was slightly more prevalent in the younger group while hypertension was more frequent among elderly patients. Previous stroke/TIA was the indication for PFO closure in 95.3% of older patients and 80.4% of younger patients, whereas other indications were more frequent among younger patients. RoPE scores were lower in older patients (median RoPE score of 5 vs. 7), and atrial septal aneurysm was more frequently detected among elderly patients. All procedures were technically successful. Procedural or in-hospital complications equally occurred in 5 (7.8%) older patients (4 AF and 1 device embolization) and 30 (7.5%) young patients (29 AF or other supraventricular arrhythmias and 1 device embolization). The follow-up duration was longer among younger patients. All-cause mortality was higher in older patients (16 deaths vs. 4 at follow-up, log-rank p < 0.001), no recurrent strokes occurred, and 2 TIAs were reported among non-elderly patients. New-onset atrial fibrillation occurred in three elderly and eight young patients. Conclusions: PFO closure is a safe procedure in patients aged ≥ 65 years, associated with favorable long-term follow-up and the prevention of ischemic neurologic recurrences.

Objective: The aim of the study is to evaluate early and long-term results of chest wall primary Ewing’s sarcoma patients treated in the time period February 2000–February 2023 by a multidisciplinary approach. Methods: We retrospectively reviewed the medical records of patients who underwent chest wall resection for a primary tumor. Treatment approach, extent of resection, 30-day mortality, overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were analyzed. Results: Overall, n = 15 consecutive patients were treated for chest wall primary Ewing’s sarcoma. A median of n = 3 ribs was resected with a median of n = 2 ribs adjacent to the lesion. Resections were extended to the adjacent structures in n = 5 patients (33.3%). In all cases, we performed a prosthetic reconstruction, associated with muscle flap (n = 10, 66.6%) or with rigid titanium bars and muscle flap (n = 6, 40%). A radical resection was accomplished in n = 13 patients (84.6%). The median surgical time was 310 ± 120 min; median hospitalization was 7.8 ± 1.9 days. Post-operative mortality was zero. We recorded n = 4 (30.7%) post-operative complication. The median follow-up (FU) was 26 months. Moreover, 5-year overall and event-free survival were 52% and 48%, respectively. Conclusions: This case series confirms the benefit of the multidisciplinary approach for Ewing sarcomas in early and long-term results.

Abstract Laser wakefield accelerators (LWFAs) can produce high-energy electron bunches in short distances. Successfully coupling these sources with undulators has the potential to form an LWFA-driven free-electron laser (FEL), providing high-intensity short-wavelength radiation. Electron bunches produced from LWFAs have a correlated distribution in longitudinal phase space: a chirp. However, both LWFAs and FELs have strict parameter requirements. The bunch chirp created using ideal LWFA parameters may not suit the FEL; for example, a chirp can reduce the high peak current required for free-electron lasing. We, therefore, design a flexible beamline that can accept either positively or negatively chirped LWFA bunches and adjust the chirp during transport to an undulator. We have used the accelerator design program MAD8 to design a beamline in stages, and to track particle bunches. The final beamline design can produce ambidirectional values of longitudinal dispersion ( $$R_{56}$$ R 56 ): we demonstrate values of + 0.20 mm, 0.00 mm and − 0.22 mm. Positive or negative values of $$R_{56}$$ R 56 apply a shear forward or backward in the longitudinal phase space of the electron bunch, which provides control of the bunch chirp. This chirp control during the bunch transport gives an additional free parameter and marks a new approach to matching future LWFA-driven FELs.

ABSTRACT Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this hypothesis, we used three antibiotics approved to treat SSTI, daptomycin, doxycycline, and vancomycin, and compared the cytotoxic effects of these antibiotics administered either before or after nsPEF. Co-treatment with nsPEF and daptomycin greatly potentiated the effects of each monotherapy regardless of their order. Conversely, the sensitivity of MRSA to both doxycycline and vancomycin was increased only when nsPEF preceded the antibiotic incubation. Finally, MRSA cells grown in biofilms were efficiently killed by co-treatment with nsPEF/vancomycin, suggesting that their mutual enhancement is maintained even when treating sessile communities known for their inherent antimicrobial resistance. Altogether our results show that MRSA perturbation by nsPEF potentiates the effect of multiple antibiotics and that the order of the combined treatment can have a major impact on efficacy. Since SSTIs are accessible for physical interventions such as nsPEF stimulus, combinatorial treatments could be used to increase the efficacy of antibiotics used to treat such infections. IMPORTANCE We have found that treatment with short electric pulses potentiates the effects of multiple antibiotics against methicillin-resistant Staphylococcus aureus. By reducing the dose of antibiotic necessary to be effective, co-treatment with electric pulses could amplify the effects of standard antibiotic dosing to treat S. aureus infections such as skin and soft-tissue infections (SSTIs). SSTIs are accessible to physical intervention and are good candidates for electric pulse co-treatment, which could be adopted as a step-in wound and abscess debridement.