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BackgroundPrior research has characterized neurodevelopmental phenotypes for Down syndrome (DS), but there is variability in age of milestone attainment and limited identification of early predictors of developmental trajectories. Additionally, less is known about receipt of education and services in relation to development.ObjectiveThis study describes the delivery of education and therapies in the setting of general developmental and behavioral needs in a large clinical cohort of children with DS seen in a specialized Down Syndrome Program (DSP).MethodThe clinically collected data included 814 patients with DS who were seen at a specialty DSP at a large, tertiary pediatric care center from March 2018 to January 2023. Data were collected through caregiver-and clinician-reported history at clinical visits to the program. Descriptive frequencies were utilized to describe participant demographics, skills and behaviors, and receipt of services, across age groups in childhood.ResultsDelays were present across all developmental domains; in particular delays in language, communication, and academic skills, and behavioral challenges were commonly reported. Almost all children received Early Intervention (EI) services, and many young children received non-public therapies after completing EI. Older participants demonstrated more impairments than younger age groups, yet received services at lower rates, particularly behavioral and speech language interventions.ConclusionA snapshot of developmental skill attainment in individuals with DS is provided. Therapies to support the levels of need were reported at much lower frequencies than the level of need reported to target aspects of development and behavior. Several gaps in therapies and educational services were identified. There is an important need for tailoring supports, based on developmental level, to meet individual needs. These findings may help to inform policy change related to developmental and educational services for individuals with DS.

Unsaturated fatty acids (UFA) play a crucial role in central cellular processes in animals, including membrane function, development, and disease. Disruptions in UFA homeostasis can contribute to the onset of metabolic, cardiovascular, and neurodegenerative disorders. Consequently, there is a high demand for analytical techniques to study lipid compositions in live cells and multicellular organisms. Conventional analysis of UFA compositions in cells, tissues, and organisms involves solvent extraction procedures coupled with analytical techniques such as gas chromatography, MS and/or NMR spectroscopy. As a nondestructive and nontargeted technique, NMR spectroscopy is uniquely capable of characterizing the chemical profiling of living cells and multicellular organisms. Here, we use NMR spectroscopy to analyze Caenorhabditis elegans, enabling the determination of their lipid compositions and fatty acid unsaturation levels both in cell-free lipid extracts and in vivo. The NMR spectra of lipid extracts from WT and fat-3 mutant C. elegans strains revealed notable differences due to the absence of Δ-6 fatty acid desaturase activity, including the lack of arachidonic and eicosapentaenoic acyl chains. Uniform 13C-isotope labeling and high-resolution 2D solution-state NMR of live worms confirmed these findings, indicating that the signals originated from fast-tumbling lipid molecules within lipid droplets. Overall, this strategy permits the analysis of lipid storage in intact worms and has enough resolution and sensitivity to identify differences between WT and mutant animals with impaired fatty acid desaturation. Our results establish methodological benchmarks for future investigations of fatty acid regulation in live C. elegans using NMR.

ObjectiveThe aim of the present retrospective study was to compare the changes resulting from treatment using the MA and the TB with special regard to the oro-and naso-pharyngeal sagittal airway dimensions in subjects with dentoskeletal Class II malocclusions and positive history of Sleep Disorder Breathing (SDB) diagnosed through the Pediatric Sleep Questionnaire (PSQ).Materials and methodsThis retrospective study involved 2 groups of subjects: patients treated with Twin Block (TB group: n = 22, 10 males, 12 females; mean age 12.0 ± 1.3 years) and patients treated with Mandibular Advancement (MA group: n = 23, 11 males, 12 females; mean age 12.2 ± 1.1 years). Pretreatment (T1) and posttreatment (T2) lateral cephalograms were analyzed. All patients underwent the PSQ to diagnose SDB.ResultsIn both treated groups there was an increase in the airways dimensions and an improvement in symptoms related SDB. The statistical comparison of the changes between T1 and T2 in the TB group showed a significant increment in upper airway size (PNS-AD2, +1.50 mm + −3.30; McNamara's upper pharynx dimension, +2.21 + −4.21) after active treatment. The MA group showed similar results during active treatment with a significant increase in both upper (PNS-AD2, +2.72 + −2.65; McNamara's upper pharynx dimension, +2.97 + −3.07) and lower (PNS-AD1, +2.17 mm + −3.54) airway size.ConclusionsDespite the different structure of these two devices and the different advancement protocols, both appliances were valuable as a suitable treatment option for Class II patients with respiratory disorders, inducing an increase of upper and lower airway size and a significant reduction in diurnal symptoms.

BackgroundFNDs mimicking a stroke represent a growing challenge in the emergency department (ED). A comprehensive diagnostic approach involving clinical evaluation and neuroimaging is essential to differentiate stroke from mimics. The safety profile of thrombolysis justifies its use where FNDs cannot be ruled out. This approach highlights the need for more precise diagnostic tools and protocols to improve patient care and reduce unnecessary treatments. Distinguishing FNDs from actual cerebrovascular events is critical yet difficult, particularly under time constraints. Given the urgency and potential severity of strokes, intravenous thrombolysis is frequently administered even when FNDs cannot be definitively excluded.MethodsThis retrospective study analyzed data of participants admitted to the Trieste University Hospital Stroke Unit between January 2018 and December 2022, focusing on those presenting with sudden-onset focal neurological deficits mimicking a stroke, with some presenting within the reperfusion treatment window (

Fatty acid composition is an essential aspect of the qualitative assessment of olive oil. A method for evaluating and trending fatty acid composition of olive varieties directly from a limited amount of drupes, has been proven reliable in comparison with traditional oil analysis. No significant difference was detected between the two methods for the 27 cultivars tested, despite presenting decidedly different acid compositions. The results obtained, crossed with those of oil yield, can represent a useful resource to set the harvest calendars by choosing the most suitable time for the production of superior quality oils and for reducing the risk of pathogen infections or pest attack. For three cultivars, the acid composition was evaluated during three ripening phases (green, veraisoned and veraisoned to black). The different behaviors suggest it is the genotype that determines this -still little known- physiological trait in olive. An interesting finding was that the oils from drupes harvested in August showed linolenic acid values higher than the limit (1.00%) set in the international standards for the classification of olive oils, requesting further investigation.

Summary: Three-dimensional (3D) ex vivo cultures allow the study of cancer progression and drug resistance mechanisms. Here, we present a protocol for measuring on-target drug sensitivity in a scaffold-free 3D culture system through quantification of apoptotic tumor cells. We provide detailed steps for sample processing, immunofluorescence staining, semi-high-throughput confocal imaging, and imaged-based quantification of 3D cultures. This protocol is versatile and can be applied in principle to any patient-derived material. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Acute myeloid leukemia (AML) is associated with poor outcomes in older adults. A major goal of treatment is to balance quality of life and functional independence with disease control. With the approval of new, more tolerable regimens, more older adults are able to receive AML-directed therapy. Among these options are hypomethylating agents (HMAs), specifically azacitidine and decitabine. HMAs have become an integral part of AML therapy over the last two decades. These agents are used either as monotherapy or nowadays more commonly in combination with other agents such as the Bcl-2 inhibitor venetoclax. Biological AML characteristics, such as molecular and cytogenetic risk factors, play crucial roles in guiding treatment decisions. In patients with high-risk AML, HMAs are increasingly used rather than intensive chemotherapy, although further trials based on a risk-adapted approach using patient- and disease-related factors are needed. Here, we review trials and evidence for the use of HMA monotherapy and combination therapy in the management of older adults with AML. Furthermore, we discuss the use of HMAs and HMA combination therapies in AML, mechanisms of action, their incorporation into hematopoietic stem cell transplantation strategies, and their use in patients with comorbidities and reduced organ function.

Cet article aborde les différentes manières dont Rodolfo Walsh recourt au journalisme. En s’appuyant sur ces formes journalistiques et ses enquêtes, nous tentons de définir ce que Rodolfo Walsh entend par écriture journalistique et quels sont les objectifs visés au moment de la publication d’un texte.

Abstract Background Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with “profound” autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. Methods Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. Results At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. Limitations Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. Conclusions By embryogenesis, the biological bases of two subtypes of ASD social and brain development—profound autism and mild autism—are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler’s social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions.

PollinERA aims to reverse pollinator population declines and reduce the harmful impacts of pesticides. It addresses the call through four objectives: SO1 filling ecotoxicological data gaps to enable realistic prediction of the source and routes of exposure and impact of pesticides on pollinators and their sensitivity to individual pesticides and mixtures. SO2 developing and testing a co-monitoring scheme for pesticides and pollinators across European cropping systems and landscapes, developing risk indicators and mixture exposure information. SO3 developing models for predicting pesticide toxicological effects on pollinators for chemicals and organisms, environmental fate, toxicokinetic/ toxicodynamic, and population models. SO4 developing a population-level systems-based approach to risk and policy assessment considering multiple stressors and long-term spatiotemporal dynamics at the landscape scale and generating an open database for pollinator/pesticide data and tools.This will be achieved through developing knowledge and protocols for a broad range of toxicological testing, feeding to in silico models (QSARS, toxicokinetic/toxicodynamic, and population). Using a strong stakeholder co-development approach, these models will be combined in a One System framework taking a systems view on risk assessment and policy evaluation, including an international monitoring program.The One System framework is based on EFSA’s system ERA view, expanding on the tools used for bees to include butterflies, moths and hoverflies. The consortium partners are experts in the field needed for this development and are well-placed to facilitate the uptake of tools by European bodies to guarantee the project's future impact.Expected impacts target Destination impacts of better understanding and addressing drivers of biodiversity decline, interconnected biodiversity research using digital technologies, and understanding the biodiversity and health nexus at the ecosystem level.

Background. The objective of this study is to establish the link between affective temperament traits and maladaptive personality traits, to verify whether the potential presence of elements related to emotional, affective and dysfunctional relational functioning can affect the couple satisfaction, modifying the well-being or discomfort condition. Materials and Methods. A data collection questionnaire was developed to investigate the factors associated with dysfunctional emotional, affective, and relational modes of functioning. The sample consisted of 473 subjects. Data were collected including the TEMPS-A questionnaire, The Dirty Dozen Italian Assessment and the Relationship Assessment Scale (RAS). Results. The findings of this study showed that the subscales of affective temperament were predictors of dark triad traits. The expressive, irritable and hyperthymic temperamental traits were found to be predictors of trait psychopathy; hyperthymic temperament is also a predictor of narcissistic traits and cyclothymic temperament is a predictor of lower couple satisfaction; men show higher scores than women in Dark triad. Conclusions. This study confirmed that temperamental traits can predict maladaptive personality traits belonging to the dark triad and confirms the importance of evaluating maladaptive personality traits to prevent forms of psychological violence in couple.

Abstract Background In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. Methods We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. Results Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. Conclusion Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Abstract Background Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight. Subjects A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, PNPLA3 was genotyped. Results Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, P

El movimiento de las personas depende de la acción del sistema nervioso sobre grupos musculares específicos que se apoyan sobre la estructura ósea. Algunos procesos patológicos pueden causar alteraciones de la fuerza y coordinación que debe existir entre las respuestas musculares, causando alteraciones en el movimiento esperado. En su fase inicial, la mayoría de estas alteraciones pasan desapercibidas hasta que los daños físicos afectan notoriamente la actividad humana, y en muchos casos de manera irreparable. Actualmente, el método más utilizado para el análisis de la marcha humana se basa en el estudio fotométrico secuencial en espacio limitado, aunque en menor medida también se utilizan sistemas de posicionamiento digital. Este proyecto aborda el desarrollo de tecnología para la captura biométrica del movimiento humano mediante sensores de medición inercial. La idea es detallar el desplazamiento espacial de secciones específicas del cuerpo a partir de la medición de aceleración y la velocidad angular, con el propósito de valorar la respuesta de las articulaciones involucradas. El objetivo es desarrollar un sistema que permita a los médicos especialistas identificar anomalías en el movimiento del paciente en estudio. Los resultados preliminares demuestran la eficiencia del sensor inercial implementado. Utilizando 7 sensores ubicados estratégicamente en el cuerpo del paciente y con una velocidad de adquisición de 100 muestras por segundo en cada sensor, es posible detallar movimientos de marcha menores a 7,5 milímetros y precisión en velocidad angular de hasta 0,1°/0,01 segundo. Con el desarrollo de este instrumento se consigue la capacidad de visualizar y analizar movimientos que normalmente son imperceptibles para el ojo humano.

Corrado Pelaia,1 Antonio Giacalone,2 Gianluca Ippolito,2 Daniela Pastore,2 Angelantonio Maglio,3 Giovanna Lucia Piazzetta,1 Nadia Lobello,1 Nicola Lombardo,1 Alessandro Vatrella,3 Girolamo Pelaia2 1Department of Medical and Surgical Sciences, University “Magna Græcia” of Catanzaro, Catanzaro, Italy; 2Department of Health Sciences, University “Magna Græcia” of Catanzaro, Catanzaro, Italy; 3Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, ItalyCorrespondence: Corrado Pelaia, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Viale Europa – Località Germaneto, Catanzaro, 88100, Italy, Tel + 39 0961 3647007, Email pelaia.corrado@gmail.comAbstract: Many different phenotypes that characterize severe asthma are supported by intricate pathomechanisms called endotypes. The latter are driven by molecular interactions, mediated by intercellular networks. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, real-world studies have confirmed the positive effects of currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as the receptors of interleukins-4 (IL-4) and 13 (IL-13). The best way to treat severe asthma should be chosen based on the peculiar phenotypic and endotypic traits of each patient. This will lead to relevant improvements in both clinical and functional outcomes. In particular, biological therapies can change the lives of asthma patients with a strong impact on quality of life. Unfortunately, patients with severe non-type-2 asthma, who continue to have pertinent unmet needs, are not receiving satisfactory advances within the context of biological treatments. It is also hopeful that in the next future new therapeutic strategies will be specifically implemented for these people, perhaps offering them the opportunity to improve their current, mostly inadequate asthma management.Keywords: type 2 severe asthma, monoclonal antibodies, pro-inflammatory cytokines, quality of life

Abstract Introduction Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. Methods One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. Results Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1–Q3) of 10 (6–19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. Conclusions Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

Abstract Aims Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy. Methods Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion. The study endpoints were i) incidence of cancer therapy-related cardiac dysfunction (CTRCD), CTRCD were also balanced for any grade CRS, but CTRCD occurred of Cardiology Guidelines on Cardio-Oncology (decrements of left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and/or elevations of cardiac biomarkers (high sensitivity troponin I, natriuretic peptides) and ii), correlations of echocardiographic metrics with inflammatory biomarkers. Results Incidence of CTRCD was high at 7 days (59,3%), particularly in subjects with CRS. The integrated definition of CTRCD allowed the identification of the majority of cases (50%). Moreover, early LVEF and GLS decrements were inversely correlated with fibrinogen and interleukin-2 receptor levels (p always ≤ 0.01). Conclusions There is a high incidence of early CTRCD in patients treated with CAR-T cells, and a link between CTRCD and inflammation can be demonstrated. Dedicated patient monitoring protocols are advised. Graphical Abstract

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival analyses utilized Kaplan–Meier curves. This was a single-institution study involving patients receiving whole-brain radiotherapy. Demographic, disease, and socioeconomic parameters from electronic medical records were collected. Morning treatment (n = 158) showed a trend toward improved overall survival vs. afternoon (n = 79); the median survival was 158 vs. 79 days (p = 0.20, HR = 0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p = 0.04) and trends in controlled primary disease (p = 0.11) and breast cancer metastases (p = 0.08) were observed. Black patients exhibited diminished circadian influence. The present study emphasized chronobiological factors’ relevance in brain metastases radiation therapy. Morning treatment correlated with improved survival, particularly in specific subgroups. Potential circadian influence disparities were identified, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

Abstract Background The individual components of mechanical ventilation may have distinct effects on kidney perfusion and on the risk of developing acute kidney injury; we aimed to explore ventilatory predictors of acute kidney failure and the hemodynamic changes consequent to experimental high-power mechanical ventilation. Methods Secondary analysis of two animal studies focused on the outcomes of different mechanical power settings, including 78 pigs mechanically ventilated with high mechanical power for 48 h. The animals were categorized in four groups in accordance with the RIFLE criteria for acute kidney injury (AKI), using the end-experimental creatinine: (1) NO AKI: no increase in creatinine; (2) RIFLE 1-Risk: increase of creatinine of > 50%; (3) RIFLE 2-Injury: two-fold increase of creatinine; (4) RIFLE 3-Failure: three-fold increase of creatinine; Results The main ventilatory parameter associated with AKI was the positive end-expiratory pressure (PEEP) component of mechanical power. At 30 min from the initiation of high mechanical power ventilation, the heart rate and the pulmonary artery pressure progressively increased from group NO AKI to group RIFLE 3. At 48 h, the hemodynamic variables associated with AKI were the heart rate, cardiac output, mean perfusion pressure (the difference between mean arterial and central venous pressures) and central venous pressure. Linear regression and receiving operator characteristic analyses showed that PEEP-induced changes in mean perfusion pressure (mainly due to an increase in CVP) had the strongest association with AKI. Conclusions In an experimental setting of ventilation with high mechanical power, higher PEEP had the strongest association with AKI. The most likely physiological determinant of AKI was an increase of pleural pressure and CVP with reduced mean perfusion pressure. These changes resulted from PEEP per se and from increase in fluid administration to compensate for hemodynamic impairment consequent to high PEEP;

Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.

Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is characterized clinically by delayed gastric emptying and upper gastrointestinal symptoms, including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric ages are very scarce. We report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle, as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with an advanced hybrid, closed loop system was successfully started. Pediatricians should consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes and appropriate symptomology.

The TANDEM project is a European initiative funded under the EURATOM program. The project started on September 2022 and has a duration of 36 months. TANDEM stands for Small Modular ReacTor for a European sAfe aNd Decarbonized Energy Mix.Small Modular Reactors (SMRs) can be hybridized with other energy sources, storage systems and energy conversion applications to provide electricity, heat and hydrogen. Hybrid energy systems have the potential to strongly contribute to the energy decarbonization targeting carbon-neutrality in Europe by 2050. However, the integration of nuclear reactors, particularly SMRs, in hybrid energy systems, is a new R&D topic to be investigated. In this context, the TANDEM project aims to develop assessments and tools to facilitate the safe and efficient integration of SMRs into low-carbon hybrid energy systems. An open-source “TANDEM” model library of hybrid system components will be developed in Modelica language which, by coupling, will extend the capabilities of existing tools implemented in the project. The project proposes to specifically address the safety issues of SMRs related to their integration into hybrid energy systems, involving specific interactions between SMRs and the rest of the hybrid systems; new initiating events may have to be considered in the safety approach.TANDEM will study two hybrid systems covering the main trends of the European energy policy and market evolution at 2035's horizon: a district heating network and power supply in a large urban area, and an energy hub serving energy conversion systems, including hydrogen production; the energy hub is inspired from a harbor-like infrastructure. TANDEM will provide assessments on SMR safety, hybrid system operationality and techno-economics. Societal considerations will also be encased by analyzing European citizen engagement in SMR technology safety.The work will result in technical, economic and societal recommendations and policy briefs on the safety of SMRs and their integration into hybrid energy systems for industry, R&D teams, Technical Safety Organizations, regulators, Non-Governmental Organizations and policy makers. The TANDEM consortium will involve 17 partners from 8 European countries (Belgium, Czech Republic, Finland, France, Germany, Italy, Spain, Ukraine).The TANDEM project has the ambition to become a pioneer initiative in Europe in gathering efforts and expertise around development of SMRs integration into hybrid energy systems. The dissemination and the exploitation of the project outcomes as well as the proposed Education & Training activities shall serve as a basis for a number of new R&D and innovation projects addressing the safety issues of SMRs and their integration into hybrid energy systems.