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Abstract A long-standing conundrum is whether age differences in personality are due to generation, or internal change with age. Using a representative sample from The Netherlands (N = 1599; aged 16–84 at the start), the current research focuses on human values (an important aspect of personality), following the same individuals for 12 years. We distinguish four generations, Silent-generation, Baby-boomers, Generation-X and Millennials. We found clear differences across generations in human values, with Millennials, e.g., valuing hedonism more than all other generations. Furthermore, value change over time was mainly evident in Millennials. Some values (achievement and conformity) were stable within individuals and between generations. Change over time across most values occurred mainly in Millennials, but not for all values. Some values were stable in adults (e.g., hedonism, conformity) while other values still increased (e.g., security, self-direction) or decreased (e.g., power, stimulation) in importance. In adults older than Millennials change decreased and change was absent in the oldest generation. Hence, age differences in values seem both due to generation, as well as internal change, although the latter mainly in young adults. These value changes over time may have implications for developments in societal values in the long run.

BackgroundAbdominal Aortic Aneurysm (AAA) is a balloon-like dilatation that can be life-threatening if not treated. Fabricating patient-specific AAA models can be beneficial for in-vitro investigations of hemodynamics, as well as for pre-surgical planning and training, testing the effectiveness of different interventions, or developing new surgical procedures. The current direct additive manufacturing techniques cannot simultaneously ensure the flexibility and transparency of models required by some applications. Therefore, casting techniques are presented to overcome these limitations and make the manufactured models suitable for in-vitro hemodynamic investigations, such as particle image velocimetry (PIV) measurements or medical imaging.MethodsTwo complex patient-specific AAA geometries were considered, and the related 3D models were fabricated through material casting. In particular, two casting approaches, i.e. lost molds and lost core casting, were investigated and tested to manufacture the deformable AAA models. The manufactured models were acquired by magnetic resonance, computed tomography (CT), ultrasound imaging, and PIV. In particular, CT scans were segmented to generate a volumetric reconstruction for each manufactured model that was compared to a reference model to assess the accuracy of the manufacturing process.ResultsBoth lost molds and lost core casting techniques were successful in the manufacturing of the models. The lost molds casting allowed a high-level surface finish in the final 3D model. In this first case, the average signed distance between the manufactured model and the reference was (−0.2±0.2) mm. However, this approach was more expensive and time-consuming. On the other hand, the lost core casting was more affordable and allowed the reuse of the external molds to fabricate multiple copies of the same AAA model. In this second case, the average signed distance between the manufactured model and the reference was (0.1±0.6) mm. However, the final model’s surface finish quality was poorer compared to the model obtained by lost molds casting as the sealing of the outer molds was not as firm as the other casting technique.ConclusionsBoth lost molds and lost core casting techniques can be used for manufacturing patient-specific deformable AAA models suitable for hemodynamic investigations, including medical imaging and PIV.

Summary: Fear-related disorders arise from inefficient fear extinction and have immeasurable social and economic costs. Here, we characterize mouse phenotypes that spontaneously show fear-independent behavioral traits predicting adaptive or maladaptive fear extinction. We find that, already before fear conditioning, specific morphological, electrophysiological, and transcriptomic patterns of cortical and amygdala pyramidal neurons predispose to fear-related disorders. Finally, by using an optogenetic approach, we show the possibility to rescue inefficient fear extinction by activating infralimbic pyramidal neurons and to impair fear extinction by activating prelimbic pyramidal neurons.

ObjectivesArterial hypertension is associated with the triggering of the renin–angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality.MethodsWe enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan–Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment.ResultsAmong the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23–0.81, p = 0.009). This association remained stable after both multivariable adjustment and propensity score matching.ConclusionIn a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment.

This paper introduces a visionary strategy, Rebalancing Regional and Remote Australia . It aims at transforming Australia into a significant global carbon sink by sequestering 4 gigatonne (Gt) of CO _2 equivalent annually, leveraging about 25% of the nation’s land area. Addressing the unique challenges of Australia’s arid climate, the plan employs innovative, proven solutions in energy, water, and agriculture, including agrivoltaics, to enhance sustainability across diverse environmental and socioeconomic contexts. A central pillar of the plan is the creation of sustainable regional and remote communities. Designed for scalability, it begins with a pilot community of 100 000 residents, showcasing the initiative’s feasibility and potential for significant return on investment. Beyond its environmental objectives, the plan presents substantial business opportunities, positioning Australia as a leader in global sustainability efforts. Through collaborative innovation, it offers a model for national and international action, highlighting the imperative for comprehensive strategies that promote economic, environmental, and social advancement.

Abstract Introduction Soft robotic wearable devices, referred to as exosuits, can be a valid alternative to rigid exoskeletons when it comes to daily upper limb support. Indeed, their inherent flexibility improves comfort, usability, and portability while not constraining the user’s natural degrees of freedom. This review is meant to guide the reader in understanding the current approaches across all design and production steps that might be exploited when developing an upper limb robotic exosuit. Methods The literature research regarding such devices was conducted in PubMed, Scopus, and Web of Science. The investigated features are the intended scenario, type of actuation, supported degrees of freedom, low-level control, high-level control with a focus on intention detection, technology readiness level, and type of experiments conducted to evaluate the device. Results A total of 105 articles were collected, describing 69 different devices. Devices were grouped according to their actuation type. More than 80% of devices are meant either for rehabilitation, assistance, or both. The most exploited actuation types are pneumatic (52%) and DC motors with cable transmission (29%). Most devices actuate 1 (56%) or 2 (28%) degrees of freedom, and the most targeted joints are the elbow and the shoulder. Intention detection strategies are implemented in 33% of the suits and include the use of switches and buttons, IMUs, stretch and bending sensors, EMG and EEG measurements. Most devices (75%) score a technology readiness level of 4 or 5. Conclusion Although few devices can be considered ready to reach the market, exosuits show very high potential for the assistance of daily activities. Clinical trials exploiting shared evaluation metrics are needed to assess the effectiveness of upper limb exosuits on target users.

Chemokines are homeostatic or inflammatory small proteins regulating immune cell migration and are structurally characterized by cysteine disulfide bridges. Around 50 human chemokines binding almost 20 seven-transmembrane G-protein coupled receptors have been discovered. The finding that two of them were the main human immunodeficiency virus (HIV) co-receptors intensified the research on the binding mechanism to block the viral entrance. Blockade of chemokine/chemokine receptor signaling ultimately modulates cell migration, then immune responses. Particular nanotechnologies can be designed to interfere with chemokine signaling or to exploit the ligand-receptor interaction. Surface chemical modification of nanomaterials with chemokines or specific peptides can find several applications in bio-medicine, from tissue-specific drug delivery to reduced cell migration in pathological conditions. Recent highlights on peculiar chemokine-nanoparticle design and their potential to modulate immune responses will be discussed.

There has been little research on the relationships between children’s personal values and the behaviors that express such values in the school context. In the present study, we examined for the first time with children at this young age, the relations between values and their value-related behaviors, i.e., supportive, disciplined, learning-oriented, and achievement-oriented, in the primary school context. The sample consisted of 952 primary school children (51.5% boys; Mage = 7.93; SD = 0.35). Data used in this study were collected in 2022 in Switzerland. A multilevel analysis confirmed the hypothesis that systematic relationships between values and teacher-rated behaviors can be demonstrated with young children. However, gender was the strongest predictor of teacher-rated children’s classroom behaviors. The results highlight the significance of understanding children’s value-behavior relations, teachers’ possible gender stereotypes of children’s behaviors, and its practical importance in the school context.

IntroductionThe use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves’ disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated.Aim of the studyWe aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH.Materials and methodsWe performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint.ResultsTwenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH.ConclusionProphylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option.

Abstract Transcatheter aortic valve implantation (TAVI) requires thorough preprocedural planning with non-invasive imaging, including computed tomography (CT). The plethora of details obtained with thoraco-abdominal CT represents a challenge for accurate and synthetic decision-making. We devised and tested a comprehensive score suitable to summarize CT exams when planning TAVI. An original comprehensive scoring system (TAVI-CT score) was devised, including details on cardiac, aortic, iliac and femoral artery features. The score was applied to a prospectively collected series of patients undergoing TAVI at our institution, driving decision making on access and prosthesis choice. Different TAVI-CT score groups were compared in terms of procedural success, acute complications, and early clinical outcomes. We included a total of 200 undergoing TAVI between February 2020 and May 2021, with 74 (37.0%) having a low (0–2) TAVI-CT score, 50 (25.0%) having a moderate (3) TAVI-CT score, and 76 (38.0%) having a high (≥ 4) TAVI-CT score. Male gender was the only non-CT variable significantly associated with the TAVI-CT score (p = 0.001). As expected, access choice differed significantly across TAVI-CT scores (p = 0.009), as was device choice, with Portico more favored and Allegra less favored in the highest TAVI-CT score group (p = 0.036). Acute outcomes were similar in the 3 groups, including device and procedural success rates (respectively p = 0.717 and p = 1). One-month follow-up showed similar rates of death, myocardial infarction, stroke, and bleeding, as well as of a composite safety endpoint (all p > 0.05). However, vascular complications were significantly more common in the highest TAVI-CT score group (p = 0.041). The TAVI-CT score is a simple scoring system that could be routinely applied to CT imaging for TAVI planning, if the present hypothesis-generating findings are confirmed in larger prospective studies.

Abstract Aims Altered mechanical load in response to injury is a main driver of myocardial interstitial fibrosis. No current in vitro model can precisely modulate mechanical load in a multicellular environment while maintaining physiological behaviour. Living myocardial slices (LMS) are a 300 μm‐thick cardiac preparation with preserved physiological structure and function. Here we apply varying degrees of mechanical preload to rat and human LMS to evaluate early cellular, molecular, and functionality changes related to myocardial fibrosis. Methods and results Left ventricular LMS were obtained from Sprague Dawley rat hearts and human cardiac samples from healthy and failing (dilated cardiomyopathy) hearts. LMS were mounted on custom stretchers and two degrees of diastolic load were applied: physiological sarcomere length (SL) (SL = 2.2 μm) and overload (SL = 2.4 μm). LMS were maintained for 48 h under electrical stimulation in circulating, oxygenated media at 37°C. In overloaded conditions, LMS displayed an increase in nucleus translocation of Yes‐associated protein (YAP) and an up‐regulation of mechanotransduction markers without loss in cell viability. Expression of fibrotic and inflammatory markers, as well as Collagen I deposition were also observed. Functionally, overloaded LMS displayed lower contractility (7.48 ± 3.07 mN mm−2 at 2.2 SL vs. 3.53 ± 1.80 mN mm−2 at 2.4 SL). The addition of the profibrotic protein interleukin‐11 (IL‐11) showed similar results to the application of overload with enhanced fibrosis (8% more of collagen surface coverage) and reduced LMS contractility at physiological load. Conversely, treatment with the Transforming growth factor β receptor (TGF‐βR) blocker SB‐431542, showed down‐regulation of genes associated with mechanical stress, prevention of fibrotic response and improvement in cardiac function despite overload (from 2.40 ± 0.8 mN mm−2 to 4.60 ± 1.08 mN mm−2). Conclusions The LMS have a consistent fibrotic remodelling response to pathological load, which can be modulated by a TGF‐βR blocker. The LMS platform allows the study of mechanosensitive molecular mechanisms of myocardial fibrosis and can lead to the development of novel therapeutic strategies.