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Equilibrated fluid-solid-growth (FSGe) is a fast, open source, three-dimensional (3D) computational platform for simulating interactions between instantaneous hemodynamics and long-term vessel wall adaptation through mechanobiologically equilibrated growth and remodeling (G&R). Such models can capture evolving geometry, composition, and material properties in health and disease and following clinical interventions. In traditional G&R models, this feedback is modeled through highly simplified fluid solutions, neglecting local variations in blood pressure and wall shear stress (WSS). FSGe overcomes these inherent limitations by strongly coupling the 3D Navier-Stokes equations for blood flow with a 3D equilibrated constrained mixture model (CMMe) for vascular tissue G&R. CMMe allows one to predict long-term evolved mechanobiological equilibria from an original homeostatic state at a computational cost equivalent to that of a standard hyperelastic material model. In illustrative computational examples, we focus on the development of a stable aortic aneurysm in a mouse model to highlight key differences in growth patterns between FSGe and solid-only G&R models. We show that FSGe is especially important in blood vessels with asymmetric stimuli. Simulation results reveal greater local variation in fluid-derived WSS than in intramural stress (IMS). Thus, differences between FSGe and G&R models became more pronounced with the growing influence of WSS relative to pressure. Future applications in highly localized disease processes, such as for lesion formation in atherosclerosis, can now include spatial and temporal variations of WSS., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Severe eosinophilic asthma (SEA) may be the prodromal phase of eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease., Objective: To identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making., Methods: A total of 30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose, and throat, and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein, IL-5, IL-4, total-IgE, IgG 4 , and antineutrophil cytoplasmic antibody), sputum (eosinophils count, periostin, IL-8, and granulocyte-monocyte colony-stimulating factor [GM-CSF]), and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used., Results: Patients with SEA had poorer asthma control (P < .001) and a higher level of sputum eosinophils (P < .002), whereas patients with EGPA reported higher levels of blood eosinophils in the past. Sputum GM-CSF was the only biomarker significantly increased in patients with EGPA compared with those with SEA (P < .0001). Among patients with SEA, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GM-CSF (P < .0005), blood, and sputum eosinophils (P < .0006 and P < .011) than the other patients., Conclusion: Sputum GM-CSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in patients with SEA, suspected of having EGPA., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Patients' perceptions of asthma symptoms, and attitudes regarding diagnosis and management, can affect their ability to reach good asthma control. The aim of the study was to explore patients' perceptions of asthma management, with focus on treatment with oral corticosteroids (OCS)., Methods: A DOXAPHARMA survey was conducted. A questionnaire with 46 multiple choice questions was completed by 50 patients with severe uncontrolled asthma, and 258 with mild-moderate controlled or partly controlled asthma. Participants were representative of Italian asthmatic patients-with medium age, long asthma duration, delayed diagnosis, poor asthma control, and frequent exacerbations., Results: Many asthmatics reported inadequate pharmacologic treatment. The majority but not all patients regularly used ICS/LABA. Oral treatment was common, mainly with OCS, particularly in severe asthmatics. One-fourth of patients did not regularly use inhaled therapy, and adherence was poor, resulting in frequent OCS use to treat exacerbations, which were common in mild-moderate cases. Patients were fairly satisfied with asthma therapies, but many had concerns about long-term corticosteroid use. Patients complained about poor management of comorbidities associated with asthma and OCS use, but were generally satisfied with their patient/doctor relationships. Many patients failed to achieve optimal health-related quality of life (HRQoL), mainly those with severe asthma who used OCS treatment and emphasized how OCS therapy impacted QoL., Conclusions: The survey results confirmed many problems related to mild-moderate and severe asthma management in Italy and highlighted the overuse of OCS rather than more effective and safe treatments, which had strong negative effects on HRQoL.

During the last years, there has been an increasing research interest in the analysis of biological fluids requiring non-invasive sampling for biomedical and clinical applications. In this work, we have focused on the nasal exudate with the aim of investigating the potential use of this fluid to know the role of iron in stroke and also for diagnosis. Potential differences in the nasal exudate, collected in swabs, from diagnosed hemorrhagic stroke, ischemic stroke, and control groups were investigated with regard to total iron by inductively coupled plasma-mass spectrometry, iron fractionation studies by size exclusion chromatography together with post-column isotope dilution analysis, and four proteins containing iron (ferritin, transferrin, lactoferrin, and ferroportin) with ELISA kits. All these analyses represent an analytical challenge, considering the rather limited amount of sample (10-40 mg) available, being the nasal exudate extracted from the swab with 300 µL 10 mM Tris/HCl, pH = 7.4. Studies to obtain reliable analytical information, such as the blank contribution of the sampling step, evaluation of the extraction efficiency of the nasal exudate from the swab, and normalization strategies for data treatment, have been carried out. Results showed that despite the limited number of investigated samples, fractionation studies as well as the concentrations of ferritin and ferroportin obtained with ELISA kits showed a differential behavior between the different cohorts., (© 2024. The Author(s).)

In situ characterization of the electric field of ultrafast pulses is critical in multiphoton microscopy. Although second harmonic generation-based collinear Frequency-Resolved Optical Gating (FROG) addresses this need, the interferometric measurement is challenged by interferometric drift instability, the required high sampling density of the acquired data, and the inability to directly use the interferometric data with conventional FROG retrieval algorithms. We address these issues by combining low-pass Fourier filtering with active kHz dithering of the interferometric path length difference using a piezo-driven retroreflector. We demonstrate successful electric field retrieval for pulses of variable duration (∼100 fs-3 ps), in situ characterization of a chirped pulse in a nonlinear microscope, and a significant reduction in acquisition time, without loss of resolution, by undersampling.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by joint destruction and extra-articular manifestations. Different cells and soluble components of the innate as well as adaptive immune system actively contribute to the amplification and perpetuation of the inflammatory processes and structural changes. To date, the knowledge on the mechanisms involved in RA pathogenesis is increasingly precise, mainly due to the recent data obtained from studies on genetics and molecular and cellular biology. In this review article we summarised the new insights into RA pathogenesis from original research articles published in the last year.

Objective: Initiated by the Severe Asthma Network Italy (SANI), this study aims to explore asthma patients' perceptions of disease severity, differentiating between mild and severe asthma. The objective is to identify factors influencing tailored treatment strategies for varying disease severities and to provide insights into asthma care in Italy., Methods: Conducted between November 2020 and January 2021, a survey using Computer-Assisted Personal Interviewing (CAPI) collected data from 308 Italian adults, representing the population. A 25 item multiple choice questionnaire covered asthma diagnosis, symptoms, treatment approaches, associated conditions, and quality of life., Results: Among participants, 83.8% reported having mild asthma, while 16.2% had severe asthma. Severe asthma patients had longer disease durations, more severe symptoms, frequent exacerbations, and higher hospital/ER visits. Although treatment adherence and symptom profiles generally aligned with international guidelines for self reported severe asthma, 22% of self identified mild asthmatics experienced severe respiratory symptoms. Oral corticosteroid (OCS) use was observed in 50% of severe cases and 22% of mild cases. Adherence was higher in severe asthma patients (76%) versus mild asthma patients (28%). Both groups experienced comorbidities, with 96% of severe asthmatics and 72% of mild asthmatics reporting impaired quality of life., Conclusion: This study highlights the disparity between clinical categorization and patient perceptions of asthma severity. The prevalence of self reported severe asthma exceeds literature data. The burden of mild asthma remains significant, with treatment approaches not fully aligned, particularly regarding disproportionate OCS use. Addressing this gap requires enhancing patient education, improving diagnostic practices, and promoting adherence., Competing Interests: FB received financial grants from AstraZeneca, Chiesi Farmaceutici S.p.A and Insmed Inc.; he worked as a paid consultant for Menarini and Zambon; and received speaker fees from AstraZeneca, Chiesi Farmaceutici S.p.A., GlaxoSmithKline, Guidotti, Grifols, Insmed Inc., Menarini, Novartis AG, SanofiGenzyme, Viatris Inc., Vertex Pharmaceuticals and Zambo; CM received grants from AZ, GSK, Sanofi; GWC reports having received research grants as well as being lecturer or having received advisory board fees from: A. Menarini, Allergy Therapeutics, AstraZeneca, Chiesi Farmaceutici, Faes, Firma, GuidottiMalesci, Glaxo Smith Kline, Hal Allergy, Innovacaremd, Novartis, OmPharma, RedMaple, SanofiAventis, SanofiGenzyme, StallergenesGreer, Uriach Pharma, ThermoFisher, Valeas; EH received a research grant from GlaxoSmith&Kline, and fees for lectures from Sanofi, Regeneron, GlaxoSmith&Kline, AstraZeneca, Novartis, Chiesi, StallergenesGreer; and declares fees for advisory boards participation from Sanofi, Regeneron, Glaxo Smith Kline, AstraZeneca, Novartis, Chiesi, Almirall, Celltrion Healthcare, Bosch; PP received advisory board fees from Chiesi Farmaceutici, Glaxo Smith Kline, and Sanofi, and fees for educational activities from: AstraZeneca, Chiesi Farmaceutici, Glaxo Smith Kline, Guidotti and Sanofi; GS received grants from AZ, GSK, Sanofi, Novartis. The authors declare that they have no relevant conflicts of interest for the present manuscript., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C 6 and cepham C 7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b , which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB., Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05)., Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved., Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy., Competing Interests: Conflict of Interest: Rehan J. Haidry declares: Pentax Medical, Apollo Endosurgery, Medtronic, Odin Vision, Cook Endoscopy, Fractyl Limited, Endogastric Solutions; Enrique Rodríguez de Santiago declares: Olympus, Norgine and Apollo Endosurgery (Educational activities) Adacyte therapeuthics (Advisory); Seth A. Gross declares: Cook, Medtronic, Olympus, Microtech. The other authors have nothing to declare, (Copyright: © 2024 Hellenic Society of Gastroenterology.)

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV 1 ) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

Background: The objective of the present study is to analyze the epidemiological, clinical and functional characteristics of patients admitted to the University Hospital of Navarra due to SARS-CoV-2 infection, as well as the predictors of mortality, during the first wave of the pandemic caused by this virus., Methodology: An observational, retrospective study was performed, including all hospitalized patients older than 75 years. Information has been obtained on multiple variables, among which it is worth mentioning previous geriatric syndromes or those that have appeared during hospitalization, or past medical history considered relevant in SARS-CoV-2 infection. A descriptive analysis of the data, comparisons according to various factors of interest and multivariate analysis to analyze factors associated with mortality were carried out., Results: Data have been obtained from a total of 426 patients with a mean age of 83.2 years (52.6% men). 34.7% died in hospital and 4.5% within 1 month after hospital discharge. The factors related to mortality were: worse baseline functional status, chronic kidney disease, and fever or dyspnea as forms of presentation. The most frequent typical symptoms were: fever, dyspnea, cough, asthenia and hyporexia. Up to 42.1% presented delirium as a symptom of atypical onset. We observed a functional deterioration that was not recover after a month of follow-up (baseline Barthel index 81.12; 70.08 at discharge; 75.55 after a month)., Conclusions: SARS-CoV-2 infection has caused high mortality rates in older adults. In this age group, the atypical presentation of this disease and functional deterioration during hospitalization are frequent. In the present study, a worse previous functional status has been identified as a predictor of mortality. More studies are needed to evaluate the impact that the disease and hospitalization have on the older patient, with the aim of implementing preventive, diagnostic and therapeutic measures that are necessary to avoid functional deterioration and adverse health events related to it., (Copyright © 2023 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided., (Copyright © 2024 by The American College of Gastroenterology and the Radiological Society of North America.)

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology . The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.

Multiple sclerosis (MS) is a chronic demyelinating disease, whose etiology is not yet fully understood, although there are several factors that can increase the chances of suffering from it. These factors include nutrition, which may be involved in the pathogenesis of the disease. In relation to nutrition, docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), has emerged as an important player in the regulation of neuroinflammation, being considered a pleiotropic molecule. This study aimed to evaluate the effect of DHA supplementation on clinical state and oxidative stress produced by experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Twenty-five Dark Agouti rats which were used divided into Control Group, Control+Vehicle Group, Control+DHA Group, EAE Group, and EAE+DHA Group. DHA was administered for 51 days by intraperitoneal (i.p.) injection at a dose of 40 mg/kg, once a day, 5 days a week. DHA supplementation produced a decrease in oxidative stress, as well as an improvement in the clinical score of the disease. DHA could exert a beneficial effect on the clinic of MS, through the activation of the antioxidant factor Nrf2., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: The high-salt diet (HSD) has been associated with cognitive dysfunction by attacking the cerebral microvasculature, through an adaptive response, initiated in the intestine and mediated by Th17 cells. In the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), it has been described that NaCl causes an increase in T cell infiltration in the central nervous system. NaCl also promotes macrophage response and Th17 cell differentiation, worsening the course of the disease. HSD may trigger an activation of the immune system and enhance inflammation. However, certain studies not only do not support this possibility, but support the opposite, as the effect of salt on immune cells may not necessarily be pathogenic. Therefore, this study aimed to evaluate the effect of an over intake of salt in rats with EAE, based on the clinical course, oxidative stress, markers of inflammation and the gut dysbiosis. Methods: 15 Dark Agouti rats were used, which were divided into control group, EAE group and EAE + NaCl group. Daily 0.027 g of NaCl dissolved in 300 μl of H 2 O was administered through a nasogastric tube for 51 days. Results: NaCl administration produced an improvement in clinical status and a decrease in biomarkers of oxidative stress, inflammation, and dysbiosis. Conclusion: The underlying mechanism by which NaCl causes these effects could involve the renin-angiotensin-aldosterone system (RAAS), which is blocked by high doses of salt.

We implement full, three-dimensional constrained mixture theory for vascular growth and remodeling into a finite element fluid-structure interaction (FSI) solver. The resulting "fluid-solid-growth" (FSG) solver allows long term, patient-specific predictions of changing hemodynamics, vessel wall morphology, tissue composition, and material properties. This extension from short term (FSI) to long term (FSG) simulations increases clinical relevance by enabling mechanobioloigcally-dependent studies of disease progression in complex domains., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Constrained Mixture Model (CMM) is a novel approach to describe arterial wall mechanics, whose formulation is based on a referential physiological state. The CMM considers the arterial wall as a mixture of load-bearing constituents, each of them with characteristic mass fraction, material properties, and deposition stretch levels from its stress-free state to the in-vivo configuration. Although some reports of this model successfully assess its capabilities, they barely explore experimental approaches to model patient-specific scenarios. In this sense, we propose an iterative fitting procedure of numerical-experimental nature to determine material parameters and deposition stretch values. To this end, the model has been implemented in a finite element framework, and it is calibrated using reported experimental data of descending thoracic aorta. The main results obtained from the proposed procedure consist of a set of material parameters for each constituent. Moreover, a relationship between deposition stretches and residual strain measurements (opening angle and axial stretch) has been numerically proved, establishing a strong consistency between the model and experimental data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Navarrete, Utrera, Rivera, Latorre, Celentano and García-Herrera.)

Introduction: Many mental disorders especially chronic serious ones such as schizophrenia-spectrum disorders, are disabling syndromes and impact on patients' social and cognitive functioning, including work activity. Thus, affected patients may show a particular socio-economic vulnerability and need specific social security as well as rehabilitation interventions, including pensions or job-placements. In Italy, the Working Group named 'Employment and Social Security/Insurance in Mental Health (ESSIMH)' was founded in 2020 in order to collect research evidence on mental illness, employment, social security, and rehabilitation., Methods: A descriptive, observational and multi-center study has been conducted in eleven Departments of Mental Health in Italy (Foggia, Brindisi, Putignano, Rome, Bologna, Siena, Pavia, Mantova, Genova, Brescia, and Torino) and involved 737 patients affected by major mental illness and classified in five diagnostic categories: psychoses, mood disorders, personality disorders, anxiety disorders, and others. The data collection was performed in 2020 among patients aged 18 to 70 years old., Results: The rate of employment in our sample was 35.8% ( n  = 264). Occupational disability in our sample was recognized in 58.0% of patients with a mean percentage of severity 51.7 ± 43.1; patients with psychoses (73%) reported higher disability followed by personality (60%) and mood disorders (47.3%) ones. In a logistic multivariate modeling, factors significantly associated with diagnosis were (a) higher level of occupational disability in psychoses; (b) higher number of job- placement programs among psychoses patients; (c) lower level of employment in psychoses; (d) more psychotherapy in personality disorder patients; and (e) more years of MHC program in psychoses patients; factors associated with sex were: (a) higher number of drive licenses among males; (b) more physical activity among males; and (c) higher number of job-placement programs among males., Conclusion: patients affected by psychoses were more likely to be unemployed, reported higher occupational disability as well as received more incentives and rehabilitation interventions. These findings confirmed that schizophrenia-spectrum disorders are disabling and patients need psychosocial support and interventions in the framework of a recovery-oriented treatment., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pregnancy associates with dramatic changes in maternal cardiovascular physiology that ensure that the utero-placental circulation can support the developing fetus. Particularly striking is the marked flow-induced remodeling of uterine arteries during pregnancy and their recovery following birth. Whereas details are available in the literature on alterations in hemodynamics within and changes in the dimensions of uterine arteries during and following pregnancy in mice, we report here the first biaxial biomechanical phenotyping of these arteries during this dynamic period of growth and remodeling (G&R). To gain additional insight into the measured G&R, we also use a computational constrained mixture model to describe and predict findings, including simulations related to complications that may arise during pregnancy. It is found that dramatic pregnancy-induced remodeling of the uterine artery is largely, but not completely, reversed in the postpartum period, which appears to be driven by increases in collagen turnover among other intramural changes. By contrast, data on the remodeling of the ascending aorta, an elastic artery, reveal modest changes that are fully recovered postpartum. There is strong motivation to continue biomechanical studies on this critical aspect of women's health, which has heretofore not received appropriate consideration from the biomechanics community., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Blood vessels grow and remodel in response to mechanical stimuli. Many computational models capture this process phenomenologically, by assuming stress homeostasis, but this approach cannot unravel the underlying cellular mechanisms. Mechano-sensitive Notch signaling is well-known to be key in vascular development and homeostasis. Here, we present a multiscale framework coupling a constrained mixture model, capturing the mechanics and turnover of arterial constituents, to a cell-cell signaling model, describing Notch signaling dynamics among vascular smooth muscle cells (SMCs) as influenced by mechanical stimuli. Tissue turnover was regulated by both Notch activity, informed by in vitro data, and a phenomenological contribution, accounting for mechanisms other than Notch. This novel framework predicted changes in wall thickness and arterial composition in response to hypertension similar to previous in vivo data. The simulations suggested that Notch contributes to arterial growth in hypertension mainly by promoting SMC proliferation, while other mechanisms are needed to fully capture remodeling. The results also indicated that interventions to Notch, such as external Jagged ligands, can alter both the geometry and composition of hypertensive vessels, especially in the short term. Overall, our model enables a deeper analysis of the role of Notch and Notch interventions in arterial growth and remodeling and could be adopted to investigate therapeutic strategies and optimize vascular regeneration protocols., (© 2023. The Author(s).)

Oxidative stress is heavily involved in several pathological features of Multiple Sclerosis (MS), such as myelin destruction, axonal degeneration, and inflammation. Different therapies have been shown to reduce the oxidative stress that occurs in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Some of these therapies are transcranial magnetic stimulation (TMS), extra virgin olive oil (EVOO) and S-allyl cysteine (SAC). This study aims to test the antioxidant effect of these three therapies, to compare the efficacy of SAC versus TMS and EVOO, and to analyze the effect of combining SAC + TMS and SAC and EVOO. Seventy Dark Agouti rats were used, which were divided into Control group; Vehicle group; Mock group; SAC; EVOO; TMS; SAC + EVOO; SAC + TMS; EAE; EAE + SAC; EAE + EVOO; EAE + TMS; EAE + SAC + EVOO; EAE + SAC + TMS. The TMS consisted of an oscillatory magnetic field in the form of a sine wave with a frequency of 60 Hz and an amplitude of 0.7mT (EL-EMF) applied for two hours in the morning, once a day, five days a week. SAC was administered at a dose of 50 mg/kg body weight, orally daily, five days a week. EVOO represented 10% of their calorie intake in the total standard daily diet of rats AIN-93G. All treatments were maintained for 51 days. TMS, EVOO and SAC, alone or in combination, reduce oxidative stress, increasing antioxidant defenses and also lowering the clinical score. Combination therapies do not appear to be more potent than individual therapies against the oxidative stress of EAE or its clinical symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Polypharmacy is a common condition among older adults and is associated with adverse drug reactions and health outcomes, including falls, functional and cognitive impairment, and frailty., Methods: A prospective observational study will be conducted on older adults with polypharmacy. The aim is to assess the impact of a specialized outpatient clinic focused on pharmacotherapy optimization recently integrated into daily clinical practice in a Spanish public tertiary teaching hospital on patients' functional and cognitive abilities. Patients who attend a first consultation and meet inclusion criteria (≥75 years old, have a life expectancy≥3 months, and polypharmacy (≥5 prescribed medications) will be invited to participate in the study, until reach a calculated sample size of 104 participants. Patients will be excluded if they are enrolled in a clinical trial related to medication or in the event of a no-show or cancellation of the appointment at the first visit. Participants will receive usual care: a first consultation including multidisciplinary pharmacological optimization in the context of a CGA and subsequent face-to-face and/or telephone follow-up (∼3 and ∼6 months). The primary endpoint will be the functional (Barthel index) and cognitive change in capacities (IPCR - Índice de Incapacidad psíquica de la Cruz Roja). Secondary endpoints include medication changes, changes in patients' quality of life, rate of falling, and use of healthcare resources., Discussion: We expect that the close collaboration between professionals from different disciplines working together will be an effective strategy to improve the functional and cognitive abilities of older adults., Trial Registration: ClinicalTrials.gov: NCT05408598 (March 1, 2022)., (Copyright © 2023 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases., Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated., Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis ( p <0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits ( p <0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD., Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD., Competing Interests: AJ-P is employee of Quibim SL. AA-B is CEO and shareholder of Quibim SL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marti-Aguado, Ten-Esteve, Baracaldo-Silva, Crespo, Coello, Merino-Murgui, Fernandez-Paton, Alfaro-Cervello, Sánchez-Martín, Bauza, Jimenez-Pastor, Perez-Girbes, Benlloch, Pérez-Rojas, Puglia, Ferrández, Aguilera, Latorre, Monton, Escudero-García, Bosch-Roig, Alberich-Bayarri and Marti-Bonmati.)

Background: No consensus is available regarding which radiographic measurement most accurately correlates with anterior coverage of the femoral head., Purpose: (1) To determine the correlation between 2 measurements of anterior wall coverage: total anterior coverage (TAC) calculated from radiographs and equatorial anterior acetabular sector angle (eAASA) calculated from computed tomography (CT) scans; (2) to define the correlation between anterior center-edge angle (ACEA) and anterior wall index (AWI) with TAC and eAASA; and (3) to investigate what other radiographic metrics may help predict anterior coverage., Study Design: Cohort study (Diagnosis); Level of evidence, 3., Methods: The authors retrospectively reviewed 77 hips (48 patients) for which radiographs and CT scans were obtained for reasons other than hip-related pain. Mean age of the population was 62 ± 22 years; 48 (62%) hips were from female patients. Two observers measured lateral center-edge angle (LCEA), AWI, Tönnis angle, ACEA, CT-based pelvic tilt, and CT-based acetabular version, with all Bland-Altman plots within 95% agreement. Correlation between intermethod measurements was estimated with a Pearson coefficient. Linear regression was used to test the ability of baseline radiographic measurements to predict both TAC and eAASA., Results: Pearson coefficients were r = 0.164 (ACEA vs TAC; P = .155), r = 0.170 (ACEA vs eAASA; P = .140), r = 0.58 (AWI vs TAC; P = .0001), and r = 0.693 (AWI vs eAASA; P < .0001). Multiple linear regression model 1 showed that AWI (β = 17.8; 95% CI, 5.7 to 29.9; P = .004), CT acetabular version (β = -0.45; 95% CI, -0.71 to -0.22; P = .001), and LCEA (β = 0.33; 95% CI, 0.19 to 0.47; P = .001) were useful to predict TAC. Multiple linear regression model 2 revealed that AWI (β = 25; 95% CI, 15.67 to 34.4; P = .001), CT acetabular version (β = -0.48; 95% CI, -0.67 to -0.29; P = .001), CT pelvic tilt (β = 0.26; 95% CI, 0.12 to 0.4; P = .001), and LCEA (β = 0.21; 95% CI, 0.1 to 0.3; P = .001) accurately predicted eAASA. Model-based estimates and 95% CIs using 2000 bootstrap samples from the original data were 6.16 to 28.6 for AWI in model 1 and 15.1 to 34.26 for AWI in model 2., Conclusion: There was a moderate to strong correlation between AWI and both TAC and eAASA, whereas ACEA correlated weakly with the former measurements, thus not being useful to quantify anterior acetabular coverage. Other variables such as LCEA, acetabular version, and pelvic tilt may also help predict anterior coverage in asymptomatic hips.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Hospital-based specialty-trained physicians have become more prevalent with emerging data suggesting benefit in consult and procedure volume, reduced complication rates, and increased practice productivity. Interest in gastroenterology (GI) hospitalist programs has increased in recent years. However, little is known regarding the types of GI hospitalist models that currently exist., Aims: To characterize the infrastructure of GI hospitalist models across the USA., Methods: A 50-question survey was distributed to the GI Hospitalist Special Interest Group of the American Society for Gastrointestinal Endoscopy. Information on demographics, hospital infrastructure, and compensation were collected., Results: 31 of 33 (94%) GI hospitalists completed the questionnaire. Respondents were mostly male (65%), white (48%) or Asian (42%). Most GI hospitalists spent at least half of their clinical time dedicated to the inpatient consultation service (73%), during which they had no other clinical duties. Most services had endoscopy suites with dedicated inpatient endoscopy rooms (66%), over 4 h allotted for procedures (83%), and were available on weekends (62%). Over half of GI hospitalists reported having outpatient duties, the most common being performance of direct access endoscopy (69%). Outside of clinical responsibilities, GI hospitalists were most frequently involved in clinical education or fellowship program leadership (48%). Most GI hospitalists were salaried with an incentive-based bonus based on work relative value units., Conclusion: GI hospitalist programs are varied throughout the USA but key commonalities exist between most programs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Soil microorganisms are in constant interaction with plants, and these interactions shape the composition of soil bacterial communities by modifying their environment. However, little is known about the relationship between microorganisms and native plants present in extreme environments that are not affected by human intervention. Using high-throughput sequencing in combination with random forest and co-occurrence network analyses, we compared soil bacterial communities inhabiting the rhizosphere surrounding soil (RSS) and the corresponding bulk soil (BS) of 21 native plant species organized into three vegetation belts along the altitudinal gradient (2400-4500 m a.s.l.) of the Talabre-Lejía transect (TLT) in the slopes of the Andes in the Atacama Desert. We assessed how each plant community influenced the taxa, potential functions, and ecological interactions of the soil bacterial communities in this extreme natural ecosystem. We tested the ability of the stress gradient hypothesis, which predicts that positive species interactions become increasingly important as stressful conditions increase, to explain the interactions among members of TLT soil microbial communities., Results: Our comparison of RSS and BS compartments along the TLT provided evidence of plant-specific microbial community composition in the RSS and showed that bacterial communities modify their ecological interactions, in particular, their positive:negative connection ratios in the presence of plant roots at each vegetation belt. We also identified the taxa driving the transition of the BS to the RSS, which appear to be indicators of key host-microbial relationships in the rhizosphere of plants in response to different abiotic conditions. Finally, the potential functions of the bacterial communities also diverge between the BS and the RSS compartments, particularly in the extreme and harshest belts of the TLT., Conclusions: In this study, we identified taxa of bacterial communities that establish species-specific relationships with native plants and showed that over a gradient of changing abiotic conditions, these relationships may also be plant community specific. These findings also reveal that the interactions among members of the soil microbial communities do not support the stress gradient hypothesis. However, through the RSS compartment, each plant community appears to moderate the abiotic stress gradient and increase the efficiency of the soil microbial community, suggesting that positive interactions may be context dependent., (© 2023. The Author(s).)

Introduction: Parkinson's disease (PD) is characterized by high-rates of depression with limited evidence-based treatment options to improve mood. Objective: To expand therapeutic options, we evaluated the feasibility and effect of a telehealth mindfulness-based cognitive therapy intervention adapted for PD (MBCT-PD) in a sample of participants with DSM-5 depressive disorders. Methods: Fifteen participants with PD and clinically-significant depression completed 9 sessions of MBCT-PD. Depression, anxiety, and quality of life were evaluated at baseline, endpoint, and 1-month follow-up. Results: Telehealth MBCT-PD was feasible and beneficial. Completion rates exceeded 85% and treatment satisfaction rates were high. Notable improvements were observed for depression, anxiety, and quality of life over the course of the trial. Conclusion: Telehealth MBCT-PD shows promise and warrants further evaluation via randomized clinical trial with more diverse participants. Such research holds the potential to expand the range of therapeutic options for depression in PD, thereby setting the stage for personalized care.

The brewing activity in Andean Patagonia plays a very important role in the region's economy, being microbial contamination one of the main problems in terms of quality. The presence of contaminant bacteria and wild yeasts in beer generate microbiological, physical and chemical changes that impact on its sensory attributes. However, few breweries establish criteria and policies to guarantee the quality of their products in a microbiological sense. The purpose of this work was to study for the first time the incidence of microbial contaminants in bottled craft beers from Andean Patagonia, identify the main microorganisms involved and establish relationships between contamination and the physicochemical variables of beer. We analyzed 75 beers from 37 breweries from 12 different Patagonian cities. Our results showed that 69.3% of the analyzed beer exhibited contaminant microorganism growth. Bacteria Levilactobacillus brevis and wild yeasts of Saccharomyces were the main microorganisms responsible for these contaminations. In addition, we found that microbial contamination had an impact on beer sensory profile and also that pH was correlated with the presence of lactic acid bacteria in beer, being an indicator of contamination for these bacteria. In conclusion, we observed that 8 out of 10 breweries studied showed contamination problems, highlighting the need to design prevention and control strategies in microbreweries., (Copyright © 2022 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Delirium is a transient neurocognitive disorder. Nonpharmacological measures can be efficient in reducing the incidence and intensity of delirium, but there is a paucity of evidence when using a physical exercise program exclusively. This was a secondary analysis of a randomised clinical trial that provided evidence on the functional and cognitive benefits of an individualised exercise intervention in hospitalised older adults. Of the 370 patients who participated in the trial, 17.1% in the intervention group had delirium and 12.1% in the control group. After the exercise intervention, 84.6% of the patients in the intervention group showed improvement in delirium compared to 68.4% of patients in the control group. Despite the fluctuating nature of delirium,we show that it is feasible to establish individualised exercise interventions in hospitalised geriatric patients in the periods when patients are able to cooperate. Baseline functional status, measured by the Barthel Index, is a clinical marker that could help to identify those who will benefit most., Competing Interests: All authors declare no Conflicts of Interest related to this manuscript.

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae , Candida albicans , Trichomonas vaginalis , and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Latorre, Gómez‐Oro, Olivera‐Valle, Blazquez‐Lopez, Gallego‐Valle, Ibañez‐Escribano, Casesnoves, González‐Cucharero, Muñoz‐Fernandez, Sanz, Vaquero, Martín‐Rabadań, Perez‐Milan and Relloso.)

Introduction: The World Health Organisation recently defined the construct of intrinsic capacity (IC), a function-based marker of older adult's health encompassing all mental and physical capacities of the individual. Multicomponent physical exercise (MCE) is a potential intervention capable to maintain/increase IC at older age; however, evidence is scarce on the effects of MCE on IC in cognitively impaired pre-frail/frail older adults., Methods: Secondary analyses of a randomised clinical trial. One hundred and eighty-eight older outpatients (age = 84.06 ± 4.77, 70.2% women) presenting with pre-frailty/frailty (according to Fried Criteria) and mild cognitive impairment (MCI)/mild dementia were recruited in the Geriatric clinics of three tertiary hospitals in Spain. Subjects were randomised to participate in the 12-week home-based individualised Vivifrail MCE or usual care. An IC index was created based on the z-score of the locomotion (Short Physical Performance Battery), cognitive (Montreal Cognitive Assessment), psychology (15-item Geriatric Depression Scale Yesavage) and vitality (handgrip strength) domains., Results: After the 3-month intervention, linear mixed models showed significant between-group differences in the evolution of the IC composite score (β=0.48; 95% confidence interval [CI] = 0.24, 0.74; P < 0.001), IC Locomotion (β = 0.42; 95% CI = 0.10, 0.74; P < 0.001), IC Cognition (β = 0.45; 95% CI = 0.03, 0.87; P < 0.05) and IC Vitality domains (β = 0.50; 95% CI = 0.25, 0.74 at 3-month) favouring the MCE group., Conclusions: The 12-week Vivifrail multicomponent exercise program is an effective strategy to enhance IC, especially in terms of locomotion, cognition and vitality IC domains in community-dwelling older adults with pre-frailty/frailty and MCI/mild dementia, compared to usual care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: follow-up studies on registries of severe/uncontrolled asthma (SUA) patients are scanty., Objective: to analyze baseline and follow-up characteristics of SUA patients and their longitudinal patterns., Methods: 180 adult patients (age ≥15 yrs) were investigated at baseline and 12-month follow-up through the Italian SUA registry (RItA). Latent transition analysis (LTA) was performed to detect cross-sectional SUA phenotypes and longitudinal patterns. Risk factors for longitudinal patterns were assessed through logistic regression., Results: a significant/borderline improvement of asthma control outcomes in the last 2-4 weeks emerged at follow-up with respect to baseline for: daily activities limitations (Δ -16%), frequent diurnal symptoms (Δ -25%), uncontrolled asthma symptoms according to ACT (Δ -26%). Last 12-month use of oral corticosteroids was less frequent at follow-up than at baseline (Δ -25%). Health status improvement was confirmed by lung function test results. Through LTA, two longitudinal patterns were detected considering last 12-month control outcomes: "persistence/worsening" (53.9%), "under control/improvement" (46.1%). A lower likelihood of having "persistence/worsening" SUA was exhibited by patients under anti-IgE (OR 0.38, 95% CI 0.17-0.84) and inhaled corticosteroids-bronchodilator association treatment (OR 0.13, 95% CI 0.01-1.26, borderline value), while a higher likelihood was shown by older age at first asthma diagnosis (OR 1.04, 95% CI 1.01-1.07)., Conclusion: the implementation of a SUA registry, the availability of patient-level data and the application of an innovative longitudinal analysis allowed to observe a general improvement in asthma control, one year after baseline, and a lower risk of SUA "persistence/worsening" in patients under anti-IgE and regular ICS-bronchodilator association use., Competing Interests: Declaration of competing interest Nicola Murgia, grants from GSK, personal fees from AstraZeneca, grants and personal fees from Chiesi, and personal fees from Menarini, outside the submitted work; Laura Carrozzi, grants for educational activities and a randomised clinical trial from GSK, Guidotti, F.I.R.M.A., Sanofi, and Chiesi, outside the submitted work; Elena Bacci, personal grants for educational activities from GSK, Sanofi, and AstraZeneca, outside the submitted work; Pier Luigi Paggiaro, personal grants for educational activities from Chiesi, GSK, Guidotti, Lusofarmaco, and Sanofi, outside the submitted work. The other authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals., Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant., Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha., Conclusions: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta)., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Epidemiological studies indicate that pre-menopausal women are more protected against the development of CVDs compared to men of the same age. This effect is attributed to the action/effects of sex steroid hormones on the cardiovascular system. In this context, estrogen modulates cardiovascular function in physiological and pathological conditions, being one of the main physiological cardioprotective agents. Here we describe the common pathways and mechanisms by which estrogens modulate the retrograde and anterograde communication between the nucleus and mitochondria, highlighting the role of genomic and non-genomic pathways mediated by estrogen receptors. Additionally, we discuss the presumable role of bromodomain-containing protein 4 (BRD4) in enhancing mitochondrial biogenesis and function in different CVD models and how this protein could act as a master regulator of estrogen protective activity. Altogether, this review focuses on estrogenic control in gene expression and molecular pathways, how this activity governs nucleus-mitochondria communication, and its projection for a future generation of strategies in CVDs treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guajardo-Correa, Silva-Agüero, Calle, Chiong, Henríquez, García-Rivas, Latorre and Parra.)

In this study, we investigated the effect of transcranial magnetic stimulation (TMS) on the ultrastructure of muscle fibers and satellite cells in rats with experimental autoimmune encephalomyelitis (EAE). EAE-induced animals were treated with TMS (60 Hz at 0.7 mT) for 2 hours in the morning, once a day, 5 days a week, for 3 weeks, starting on day 15 post-immunization. The rats were sacrificed on day 36 post-immunization, and the soleus muscles were evaluated by light microscopy and transmission electron microscopy. Findings were compared with a non-treated EAE group. Electron microscopy analysis showed the presence of degenerated mitochondria, autophagic vacuoles, and altered myofibrils in non-treated EAE group. This correlates with the presence of acid phosphatase activity in muscle fibers and core-targetoid lesions with desmin immunohistochemistry. Most myonuclei in the EAE group showed apoptotic features. In contrast, EAE induced-TMS treated animals had less ultrastructural changes in the mitochondria and the myofibrils, together with less frequent apoptotic nuclear features. Peripheral desmin+ protrusions, as a marker of active satellite cells, were significantly increased in TMS-treated group. This correlates ultrastructurally with the presence of active features in satellite cells in the TMS group. In conclusion, the attenuation of ultrastructural alterations in muscle fibers and activation response of satellite cells caused by EAE indicated that skeletal muscle had a regenerative response to TMS.

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.

Thoracic aortic aneurysm (TAA) is a localized dilatation of the aorta that can lead to life-threatening dissection or rupture. In vivo assessments of TAA progression are largely limited to measurements of aneurysm size and growth rate. There is promise, however, that computational modelling of the evolving biomechanics of the aorta could predict future geometry and properties from initiating mechanobiological insults. We present an integrated framework to train a deep operator network (DeepONet)-based surrogate model to identify TAA contributing factors using synthetic finite-element-based datasets. For training, we employ a constrained mixture model of aortic growth and remodelling to generate maps of local aortic dilatation and distensibility for multiple TAA risk factors. We evaluate the performance of the surrogate model for insult distributions varying from fusiform (analytically defined) to complex (randomly generated). We propose two frameworks, one trained on sparse information and one on full-field greyscale images, to gain insight into a preferred neural operator-based approach. We show that this continuous learning approach can predict the patient-specific insult profile associated with any given dilatation and distensibility map with high accuracy, particularly when based on full-field images. Our findings demonstrate the feasibility of applying DeepONet to support transfer learning of patient-specific inputs to predict TAA progression.

Background: Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-inflammatory biomarker of COPD. We assessed sRAGE in patients with hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap., Methods: Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers [HNS], 84 healthy smokers [HS], 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap)., Results: After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (- 12.5%, p = 0.005), COPD (- 14.8%, p < 0.001) and OSA-COPD overlap (- 12.3%, p = 0.02) compared with HNS. There were no differences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change significantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased significantly., Conclusions: The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD., (© 2022. The Author(s).)

Methods of tissue engineering continue to advance, and multiple clinical trials are underway evaluating tissue engineered vascular grafts (TEVGs). Whereas initial concerns focused on suture retention and burst pressure, there is now a pressing need to design grafts to have optimal performance, including an ability to grow and remodel in response to changing hemodynamic loads. Toward this end, there is similarly a need for computational methods that can describe and predict the evolution of TEVG geometry, composition, and material properties while accounting for changes in hemodynamics. Although the ultimate goal is a fluid-solid-growth (FSG) model incorporating fully 3D growth and remodeling and 3D hemodynamics, lower fidelity models having high computational efficiency promise to play important roles, especially in the design of candidate grafts. We introduce here an efficient FSG model of in vivo development of a TEVG based on two simplifying concepts: mechanobiologically equilibrated growth and remodeling of the graft and an embedded control volume analysis of the hemodynamics. Illustrative simulations for a model Fontan conduit reveal the utility of this approach, which promises to be particularly useful in initial design considerations involving formal methods of optimization which otherwise add considerably to the computational expense., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.

Background: Capsule endoscopy (CE) provides a novel approach to evaluate obscure gastrointestinal bleeding. Yet CE is not routinely utilized in the inpatient setting for a variety of reasons. We sought to identify factors that predict complete CE and diagnostically meaningful CE, as well as assess the impact of inpatient CE on further hospital management.1 na d2 METHODS: We conducted a retrospective review of patients undergoing inpatient CE at a tertiary referral, academic center over a 3 year period. We analyzed data on patient demographics, medical history, endoscopic procedures, hospital course, and results of CE. The primary outcome was complete CE and the secondary outcome was positive findings of pathology on CE., Results: 131 patients were included (56.5% were men 43.5% women, median age of 71.0 years). Overall, CE was complete in 77.1% of patients. Complete CE was not related to motility risk factors, gender, or administration modality. Patients with incomplete CE tended to be older, have lower BMI, and Caucasian, however results did not reach statistical significance (p = 0.06; p = 0.06; p = 0.08 respectively). Positive CE was noted in 73.3% of patients, with 35.1% of all patients having active bleeding. Positive CE was not associated with AVM risk factors or medication use. 28.0% of patients underwent subsequent hospital procedures, among which 67.6% identified the same pathology seen on CE., Conclusions: Contrary to previous studies, we found the majority of inpatient CEs were complete and positive for pathology. We found high rates of correlation between CE and subsequent procedures. The use of CE in the inpatient setting helps to guide the diagnosis and treatment of hospitalized patients with obscure gastrointestinal bleeding., (© 2022. The Author(s).)

The diversification of beer flavor is becoming increasingly popular, especially in the field of non-alcoholic beers, where sales are growing steadily. While flavor substances of traditional beers can largely be traced back to defined secondary metabolites, the production of non-alcoholic beers with non- Saccharomyces yeasts generates novel fruity flavors, some of which cannot yet be assigned to specific flavor substances. In a recently published study, besides pear, cool mint sweets, and banana-like flavor, distinctive red berry and apple flavors were perceived in a non-alcoholic beer fermented with the yeast strain Cyberlindnera saturnus TUM 247, whose secondary metabolites were to be elucidated in this study. The trials were carried out using response surface methodology to examine the fermentation properties of the yeast strain and to optimize the beer with maximum fruitiness but minimal off-flavors and ethanol content. It turned out that a low pitching rate, a moderate fermentation temperature, and an original gravity of 10.5 °P gave the optimal parameters. Qualitative analysis of the secondary metabolites, in addition to standard analysis for traditional beers, was first performed using headspace-gas chromatography with olfactometry. ( E )- β -damascenone emerged as the decisive substance for the red berry and apple flavor and so this substance was then quantitated. Although ( E )- β -damascenone is a well-known secondary metabolite in beer and this substance is associated with apple or cooked apple- and berry-like flavors, it has not yet been reported as a main flavor component in non-alcoholic beers.