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Silvia Ottaviani,1,2 Eleonora Rondanina,1,2 Floriana Arnone,3 Virna Brucato,3 Roberto Campigli,3 Massimo Della Bona,3 Luca Tagliafico,1,2 Ennio Ottaviani,4 Alessio Nencioni,1,2 Fiammetta Monacelli1,2 1Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa, 16132, Italy; 2IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 3ASL5 Ospedale San Bartolomeo, Sarzana, Italy; 4Department of Mathematics (DIMA), University of Genoa, Genoa, 16132, ItalyCorrespondence: Fiammetta Monacelli, Dipartimento di Medicina Interna e Specialità Mediche (D.I.M.I.) - Università degli Studi di Genova, Viale Benedetto XV, 6, Genova, GE, 16132, Italy, Tel/Fax +39-010-353-7545, Email fiammetta.monacelli@unige.itPurpose: In recent times, growing uncertainty has emerged regarding the effectiveness of standard pressure ulcer (PU) risk assessment tools, which are suspected to be no better than clinical judgment, especially in the frail and comorbid elderly population. This study aimed to identify the primary clinical predictive variables for PU development and severity in hospitalized older adults, utilizing a multidimensional frailty assessment, and compare them with the Braden scale.Patients and methods: The population consisted of 316 patients, admitted to the Geriatric Unit and Transitional Care of San Bartolomeo Hospital in Sarzana (Italy) during the period 21/02/22-01/07/22. The collected information included both anamnestic and laboratory data. A comprehensive geriatric assessment was performed, including also anthropometric and physical performance measurements. Multivariate logistic analysis was used, both in a binary classification test and in the subsequent ordinal classification test of severity levels. The final performance of the model was assessed by ROC curve estimation and AUC comparison with the Braden scale.Results: Within the population, 152 subjects (48%) developed PU at different levels of severity. The results showed that age, Braden scale (subscales of mobility and friction/shear), Barthel scale, Mini Nutritional Assessment, hemoglobin, and albumin are predictors associated with the development of PU (AUC 85%). The result is an improvement over the use of the Braden scale alone (AUC 75%). Regarding the identification of predictive factors for PU severity, 4AT also emerges as potentially relevant.Conclusion: Assessing the subject’s nutritional status, physical performance, and functional autonomies enables the effective integration of the Braden scale in identifying patients most susceptible to developing PU. Our findings support the integration of a comprehensive set of methodologically robust frailty determinants into traditional risk assessment tools. This integration reflects the mutual interplay between patients’ frailty, skin frailty, and PU development in very old hospitalized patients.Keywords: chronic wounds, nutrition, pressure injury, health analytics, precision medicine, chronic diseases

Abstract Images collected during NASA’s Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos’ moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of ∼10 Pa, while Dimorphos has a surface cohesion of

Abstract Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders’ fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA’s Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures’ preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

Abstract Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.

Abstract The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument onboard the Mars 2020 Perseverance rover detected so far some of the most intense fluorescence signals in association with sulfates analyzing abraded patches of rocks at Jezero crater, Mars. To assess the plausibility of an organic origin of these signals, it is key to understand if organics can survive exposure to ambient Martian UV after exposure by the Perseverance abrasion tool and prior to analysis by SHERLOC. In this work, we investigated the stability of organo-sulfate assemblages under Martian-like UV irradiation and we observed that the spectroscopic features of phthalic and mellitic acid embedded into hydrated magnesium sulfate do not change for UV exposures corresponding to at least 48 Martian sols and, thus, should still be detectable in fluorescence when the SHERLOC analysis takes place, thanks to the photoprotective properties of magnesium sulfate. In addition, different photoproduct bands diagnostic of the parent carboxylic acid molecules could be observed. The photoprotective behavior of hydrated magnesium sulfate corroborates the hypothesis that sulfates might have played a key role in the preservation of organics on Mars, and that the fluorescence signals detected by SHERLOC in association with sulfates could potentially arise from organic compounds.

IntroductionCardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms.Case descriptionWe present a case report of a 56-year-old patient with HAE-C1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%.Conclusionlanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy.

Abstract Highlanders and lowlanders of Papua New Guinea have faced distinct environmental stress, such as hypoxia and environment-specific pathogen exposure, respectively. In this study, we explored the top genomics regions and the candidate driver SNPs for selection in these two populations using newly sequenced whole-genomes of 54 highlanders and 74 lowlanders. We identified two candidate SNPs under selection - one in highlanders, associated with red blood cell traits and another in lowlanders, which is associated with white blood cell count – both potentially influencing the heart rate of Papua New Guineans in opposite directions. We also observed four candidate driver SNPs that exhibit linkage disequilibrium with an introgressed haplotype, highlighting the need to explore the possibility of adaptive introgression within these populations. This study reveals that the signatures of positive selection in highlanders and lowlanders of Papua New Guinea align closely with the challenges they face, which are specific to their environments.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals. Participants were 143 CHR individuals identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Face emotion recognition was assessed using the Penn Emotion Recognition Task (ER-40). Stigma was assessed using discrimination, stereotype awareness, and stereotype agreement subscales of the Mental Health Attitudes Interview for CHR. We tested associations of ER-40 accuracy and response times with these stigma variables, including the role of clinical and demographic factors. Racial/ethnic minoritized participants had higher attenuated positive symptoms than non-minoritized participants. Longer ER-40 response times were correlated with greater stereotype agreement (r=.17, p=.045) and discrimination (r=.22, p=.012). A regression model predicting ER-40 response times revealed an interaction of stereotype agreement with minoritized status (p=.008), with slower response times for minoritized participants as stereotype agreement increased. Greater disorganized symptoms and male gender also predicted longer response times. ER-40 accuracy was not associated with stigma. Overall, minoritized CHR individuals with greater internalized stigma took longer to identify face emotions. Future research is needed to assess whether slower response times are specific to social cues, and if internalized stigma interferes with performance in real-world social situations. Reducing stigma may be an important target for interventions that aim to improve social skills.

Tissue engineering (TE) offers promising solutions for regenerative medicine through the use of porous scaffolds and cells, providing a favorable environment for the production of functional three-dimensional (3D) tissues. However, TE strategies have faced physiological limitations with static three-dimensional culture alone, and perfusion bioreactors provide a controlled environment that better mimics native tissue. In this study, we present the optimized geometry of an existing custom-made perfusion bioreactor that utilizes an external airlift circulation loop, essentially a specially structured bubble column designed for the simultaneous allocation of multiple seeded scaffolds. By reducing volumes and materials, the optimized system maintains the same level of reliability and functionality. The study employs computational fluid dynamics (CFD) analysis and a mathematical model to gain insights into fluid flow and oxygen transport, respectively. Therefore, in line with the increasingly recognized trend of device miniaturization, scaling down the initial device would enable high-speed analysis of cellular response in perfused cultures, allowing the study of various morphologies, different cell populations, or different drug treatments. Furthermore, the possibility of creating series and parallel connections between multiple devices, while maintaining dimensions suitable for incubator insertion, demonstrates the potential of this system for testing engineered constructs while simultaneously enabling time and cost reduction compared to existing perfusion devices in the field of Tissue Engineering.

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Aim Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone.Methods International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence.Results A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021).Conclusions The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

Background Rilonacept, a once‐weekly interleukin‐1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin‐1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long‐term extension further explored recurrent pericarditis natural history and treatment duration decision‐making during 24 additional months of open‐label rilonacept treatment. Methods and Results Seventy‐four patients commenced the long‐term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off‐treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18‐month decision milestone was 0.04 events/patient‐year versus 4.4 events/patient‐year prestudy while on oral therapies. At the 18‐month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18‐month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P

The field of inflammatory disease of the heart or cardio-immunology is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

This study aims to demonstrate the possibility of incorporating a natural antioxidant biomolecule into polymeric porous scaffolds. To this end, Poly-l-Lactic Acid (PLLA) scaffolds were produced using the Thermally Induced Phase Separation (TIPS) technique and additivated with different amounts of rosmarinic acid (RA). The scaffolds, with a diameter of 4 mm and a thickness of 2 mm, were characterized with a multi-analytical approach. Specifically, Scanning Electron Microscopy analyses demonstrated the presence of an interconnected porous network, characterized by a layer of RA at the level of the pore’s surfaces. Moreover, the presence of RA biomolecules increased the hydrophilic nature of the sample, as evidenced by the decrease in the contact angle with water from 128° to 76°. The structure of PLLA and PLLA containing RA molecules has been investigated through DSC and XRD analyses, and the obtained results suggest that the crystallinity decreases when increasing the RA content. This approach is cost-effective, and it can be customized with different biomolecules, offering the possibility of producing porous polymeric structures containing antioxidant molecules. These scaffolds meet the requirements of tissue engineering and could offer a potential solution to reduce inflammation associated with scaffold implantation, thus improving tissue regeneration.