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Bruno Bordoni,1 Luca Mapelli,1 Anastasia Toccafondi,1 Francesca Di Salvo,1 Gianmarco Cannadoro,1 Matteo Gonella,1 Allan R Escher,2 Nuccia Morici1 1Dipartimento di Cardiologia, Fondazione Don Carlo Gnocchi IRCCS, Istituto di Ricovero e Cura, S Maria Nascente, Milano, 20100, Italy; 2Department of Anesthesiology/Pain Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USACorrespondence: Bruno Bordoni, Email bordonibruno@hotmail.comAbstract: Myocardial infarction (MI) is one of the leading causes of death worldwide. There can be many reasons that cause MI, such as a sedentary lifestyle, a disordered diet, harmful habits such as smoking and alcoholism, concomitant congenital or acquired systemic pathologies. Patients who survive the acute event suffer a functional alteration of multiple body systems. The various cardiology associations recommend starting a rehabilitation process, pursuing the main objective of improving the patient’s health status. A negative consequence that can be linked to MI is the dysfunction of the main breathing muscle, the diaphragm. The diaphragm is essential not only for respiratory mechanisms but also for adequate production of cardiac pressures. Post-MI patients present a reduction in the performance of the diaphragm muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. The article reviews the rehabilitation path for post-MI patients, to highlight the absence given to the diaphragm in the recovery of the patient’s health status. The text reviews the post-MI diaphragmatic adaptation to highlight the importance of including targeted training for the diaphragm muscle in the rehabilitation process.Keywords: myocardial infarction, diaphragm, cardiovascular disease, breathing, physiotherapy, cardiac rehabilitation

Abstract BackgroundConsidering the growing population of older adults, addressing the influence of loneliness among this demographic group has become imperative, especially due to the link between social isolation and deterioration of mental and physical well-being. Technology has the potential to be used to create innovative solutions to increase socialization and potentially promote healthy aging. ObjectiveThis 6-month study examined the usability and acceptability of a technology-based socialization service and explored how stress and living situation affect older adults’ and their ecosystem’s perceptions of technology, investigating cross-sectional and longitudinal differences among and across user groups. MethodsParticipants were recruited in Tuscany and Apulia (Italy) through a network of social cooperatives and a research hospital, respectively. A total of 20 older adults were provided with the same technology installed on a tablet and on a smart television. The technology has three functionalities: video calling, playing games, and sharing news. Additionally, 20 informal caregivers (IC) and 13 formal caregivers (FC) connected to the older adults were included in the study. After both initial training in the use of the system (T0) and 6 months of using the system (T6), questionnaires on usability, acceptability, and technostress were filled in by older adults, IC, and FC. Nonparametric or parametric tests were conducted to investigate group differences at both time points and changes over time. Additional analyses on older adults were done to assess whether differences in usability and acceptability were related to living situation (ie, alone or with someone). Furthermore, correlation analyses were performed between usability, acceptability, and stress toward technology at T0 and T6. ResultsAt both T0 and T6, older adults had lower usability scores than IC and FC and higher anxiety than IC. Over time, there was a significant decrease in older adults’ attitudes toward technology score, depicting a negative attitude over time (T0 median 4.2, IQR 0.5; T6 median 3.7, IQR 0.8; Cohen d ConclusionsAt the start of the study, older adults judged the system to be less usable and more stressful than did the caregivers. Indeed, at first, technostress was correlated with usability and acceptability; however, with repeated use, technostress did not influence the perception of technology. Overall, getting accustomed to technology decreased anxiety and stress toward technology.

Background: Nordic walking (NW) has several potential benefits for individuals with cardiovascular (CV) disease, type 2 diabetes, and obesity and/or overweight. NW improves cardiovascular health, including exercise capacity and blood pressure control. NW enhances glycemic control and insulin sensitivity in diabetes, and aids in weight management and body composition improvement. NW offers additional advantages, such as improvement in muscular strength, joint mobility, physical activity levels, and psychological well-being. Methods: This open-label study with 3 arms will aim to evaluate the efficacy, safety, and adherence to exercise prescription in obese and/or overweight diabetic patients with CV complications. The primary objective will be to assess the CV performance of participants after a 6-month and a 12-month follow-up period, following a 3-month NW intervention, compared with standard rehabilitation, and with cardiological counseling (control group) training lasting 3 months. Results: The results of the study will provide valuable insights into the comparative effectiveness of a NW intervention vs standard rehabilitation and control group training in improving CV performance in obese and/or overweight diabetic patients with CV complications. Additionally, safety and adherence data will help inform the feasibility and sustainability of the exercise prescription over an extended period. Conclusions: These findings may have implications for the development of tailored exercise programs for this specific patient population, with the aim of optimizing CV health outcomes. Clinical Trials Registration: NCT05987410 Résumé: Contexte: La marche nordique offre plusieurs bienfaits potentiels aux personnes atteintes d’une maladie cardiovasculaire (CV), de diabète de type 2, de surpoids ou d’obésité. Elle améliore la santé cardiovasculaire, notamment l’endurance à l’effort et la régulation de la pression artérielle, en plus de favoriser l’équilibre glycémique et d'accroître la sensibilité à l’insuline chez les personnes diabétiques. Elle facilite également la gestion du poids et l’amélioration de la composition corporelle. Par ailleurs, la marche nordique présente d’autres avantages, comme l’augmentation de la force musculaire, de la mobilité articulaire, du niveau d’activité physique et du bien-être psychologique. Méthodologie: Cette étude ouverte à 3 groupes vise à évaluer l’efficacité, la sécurité et l’observance des exercices prescrits chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Le principal objectif consistera à évaluer la performance CV des participants au cours d'une période de suivi de 6 et 12 mois après un programme de marche nordique de 3 mois, comparativement à un programme de réadaptation standard et à un programme d’encadrement en soins CV (groupe témoin) de 3 mois. Résultats: Les résultats de l’étude fourniront de précieux renseignements sur l’efficacité d’un programme de marche rapide comparativement à un programme de réadaptation standard et à un programme d’encadrement (groupe témoin) pour améliorer la performance CV chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Les données relatives à la sécurité et à l’observance permettront également d’évaluer la faisabilité et la viabilité de la prescription d’exercices sur une longue période. Conclusions: Ces résultats pourraient s’avérer utiles dans l’élaboration de programmes d’exercices spécifiquement conçus pour cette population de patients, afin d’optimiser les résultats en santé CV. Numéro d’inscription de l’essai clinique: NCT05987410

Introduction: Heart transplantation (HTx) serves as the gold-standard therapy for end-stage heart failure, yet patients often experience physical deconditioning and cognitive impairments post-surgery. Cardiac rehabilitation (CR) has shown promise in the HTx context. However, uncertainty surrounds the impact of biological sex. Accordingly, the aim of this paper was to investigate the impact of biological sex in a cohort of patients with HTx early admitted to a residential CR program. Methods: This was a retrospective analysis involving patients who underwent HTx at Niguarda Hospital and who subsequently participated in a CR program at IRCCS Fondazione Don Gnocchi, Milan, Italy, between 2010 and 2022. The primary endpoint was time to event (in months), with an event defined as a composite outcome of whichever occurred first of death, allograft rejection, or cardiac allograft vasculopathy up to 30 months follow-up. Results: In a total of 129 patients, 60 % male, and 40 % female, baseline characteristics presented comparably between the sexes. At 6 months, no significant sex differences were observed for the primary composite outcome. However, at 30 months, females exhibited a significantly lower incidence of the primary composite outcome and an increased survival rate. Multivariable analysis confirmed a protective effect of female sex against mortality (F vs. M, HR 0.164, 95 % CI 0.038–0.716, P = 0.0161). Conclusions: Despite limitations, our findings emphasize that sex affects post-HTx long-term follow-up following CR discharge, with more favorable outcomes for female recipients. In an era of tailored management algorithms, it is imperative to take into account the gender gap even in cardiac rehabilitation.

Abstract Background Once integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus. Results In this study, we examined the role of two parameters in HIV-1 LTR promoter activity. We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. Additionally, we confirmed the folding of a Guanine quadruplex (G4) structure in the HIV-1 promoter and its repressive effect. We demonstrated a direct interaction between TOP1 and this G4 structure, providing evidence of a functional relationship between the two repressive elements. Mutations abolishing G4 folding affected TOP1/G4 interaction and hindered G4-dependent inhibition of TOP1 catalytic activity in vitro. As a result, HIV-1 promoter activity was reactivated in a native chromatin environment. Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes. Conclusions Our results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. They reveal the existence of a new mechanism of TOP1/G4-dependent transcriptional repression conserved between viral and human genes. This mechanism contrasts with the known property of TOP1 as global transcriptional activator and offers new perspectives for anti-cancer and anti-viral strategies.

Bruno Bordoni,1 Allan Escher,2 Elena Compalati,1 Luca Mapelli,1 Anastasia Toccafondi1 1Department of Cardiology, Institute of Hospitalization and Care with Scientific Address, Foundation Don Carlo Gnocchi IRCCS S Maria Nascente, Milano, Italy; 2Anesthesiology/Pain Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USACorrespondence: Bruno Bordoni, Email bordonibruno@hotmail.comAbstract: Chronic obstructive pulmonary disease (COPD) is a constant and chronic narrowing of the respiratory airways, with numerous associated symptoms, not always related to the pathological adaptation of the lungs. Statistical projections show that COPD could become the third leading cause of death globally by 2030, with a significant increase in deaths by 2060. Skeletal muscle dysfunction, including the diaphragm, is one of the causes linked to the increase in mortality and hospitalization. Little emphasis is given by the scientific literature to the importance of the diaphragm towards functional neuromotor pathological expressions. The article reviews the adaptation of the skeletal muscles, with greater attention to the adaptations of the diaphragm, thereby highlighting the non-physiological variations that the main respiratory muscle undergoes and the neuromotor impairment found in COPD. The text could be an important reflection from a clinical and rehabilitation point of view, to direct greater attention to the function and adaptation of the diaphragm muscle.Keywords: diaphragm, COPD, physiotherapy, rehabilitation, pain, fascia, ageing, osteopathic

Abstract A compact broadband Edge-Line Coupler (ELC) based on Parity Time-reversal Duality (PTD) symmetry has been conceived, designed, constructed and measured. The coupler connects four PTD bifilar edge lines (BELs), recently introduced by the authors. The PTD-BELs are constituted by a parallel plate waveguide whose walls are formed by a junction between Perfect Electric Conductor (PEC) and Perfect Magnetic Conductor (PMC) boundary conditions. Reversing the axis orthogonal to the plates interchanges the position of PEC and PMC. Such a waveguide supports unimodal transverse electromagnetic (TEM) propagation, extremely confined along the top and bottom junction edges; its propagation is protected against backscattering from any discontinuity that preserves the PTD symmetry. The ELC presented here is constituted by a 4-port junction in which each port is intrinsically matched due to the PTD symmetry, strongly coupled with a second port, strongly decoupled with a third port, and weakly coupled with a fourth port. The ELC is designed by using a mushroom metasurface for the PMC portion of the device; the connection is based on a switch circuit which imposes open and short conditions on the two opposite sides of the structure. Switching simultaneously the open and short circuits reroutes the signal in a different port, while maintaining the same level of coupling with the other ports. A static prototype has been built and its measurements have confirmed the matching performance and the good directionality of the coupler in a broadband frequency range between 24 and 30 GHz.

Transmissions of simian viruses to humans has originated the different groups of HIV-1. We recently identified a functional motif (CLA), in the C-terminal domain of the integrase, essential for integration in HIV-1 group M. Here, we found that the motif is instead dispensable in group O isolates, because of the presence, in the N-terminal domain of HIV-1 O of a specific sequence, Q7G27P41H44, that we define as the NOG motif. Alterations of reverse transcription and of 3' processing observed by mutating the CLA motif of IN M are fully rescued to wt levels by inserting the sequence of the NOG motif in the N-ter of the protein. These results indicate that the two motifs (CLA and NOG) functionally complement each other and a working model accounting for these observations is proposed. The establishment of these two alternative motifs seems to be due to the different phylogenetic origin and history of these two groups. Indeed, the NOG motif is already present in the ancestor of group O (SIVgor) while it is absent from SIVcpzPtt, the ancestor of group M. The CLA motif, instead, seems to have emerged after SIVcpzPtt has been transferred to humans, since no conservation is found at the same positions in these simian viruses. These results show the existence of two-group specific motifs in HIV-1 M and O integrases. In each group, only one of the motifs is functional, potentially leading the other motif to diverge from its original function and, in an evolutionary perspective, assist other functions of the protein, further increasing HIV genetic diversity.

Summary: Background: The COVID-19 pandemic is an infectious disease caused by SARS-CoV-2. The first step of SARS-CoV-2 infection is the recognition of angiotensin-converting enzyme 2 (ACE2) receptors by the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein. Although the molecular and structural bases of the SARS-CoV-2-RBD/hACE2 interaction have been thoroughly investigated in vitro, the relationship between hACE2 expression and in vivo infection is less understood. Methods: Here, we developed an efficient SARS-CoV-2-RBD binding assay suitable for super resolution microscopy and simultaneous hACE2 immunodetection and mapped the correlation between hACE2 receptor abundance and SARS-CoV-2-RBD binding, both in vitro and in human lung biopsies. Next, we explored the specific proteome of SARS-CoV-2-RBD/hACE2 through a comparative mass spectrometry approach. Findings: We found that only a minority of hACE2 positive spots are actually SARS-CoV-2-RBD binding sites, and that the relationship between SARS-CoV-2-RBD binding and hACE2 presence is variable, suggesting the existence of additional factors. Indeed, we found several interactors that are involved in receptor localization and viral entry and characterized one of them: SLC1A5, an amino acid transporter. High-resolution receptor-binding studies showed that co-expression of membrane-bound SLC1A5 with hACE2 predicted SARS-CoV-2 binding and entry better than hACE2 expression alone. SLC1A5 depletion reduces SARS-CoV-2 binding and entry. Notably, the Omicron variant is more efficient in binding hACE2 sites, but equally sensitive to SLC1A5 downregulation. Interpretation: We propose a method for mapping functional SARS-CoV-2 receptors in vivo. We confirm the existence of hACE2 co-factors that may contribute to differential sensitivity of cells to infection. Funding: This work was supported by an unrestricted grant from “Fondazione Romeo ed Enrica Invernizzi” to Stefano Biffo and by AIRC under MFAG 2021 - ID. 26178 project – P.I. Manfrini Nicola.

Abstract Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

BackgroundInformation and communication technology solutions have the potential to support active and healthy aging and improve monitoring and treatment outcomes. To make such solutions acceptable, all stakeholders must be involved in the requirements elicitation process. Due to the COVID-19 situation, alternative approaches to commonly used face-to-face methods must often be used. One aim of the current article is to share a unique experience from the Pharaon project where due to the COVID-19 outbreak alternative elicitation methods were used. In addition, an overview of common functional, quality, and emotional goals identified by six pilot sites is presented to complement the knowledge about the needs of older adults.MethodsOriginally planned face-to-face co-creation seminars were impossible to carry out, and all pilot sites chose alternative requirements elicitation methods that were most suitable in their situation. The elicited requirements were presented in the form of goal models. In one summary goal model, we provide an overview of common functional, quality, and emotional goals.ResultsDifferent elicitation methods were combined based on the digital literacy of the target group and their access to digital tools. Methods applied without digital technologies were phone interviews, reviews of literature and previous projects, while by means of digital technologies online interviews, online questionnaires, and (semi-)virtual co-creation seminars were conducted. The combination of the methods allowed to involve all planned stakeholders. Virtual and semi-virtual co-creation seminars created collaborative environment comparable to face-to-face situations, while online participation helped to save the time of the participants. The most prevalent functional goals elicited were “Monitor health,” “Receive advice,” “Receive information.” “Easy to use/comfortable,” “personalized/tailored,” “automatic/smart” were identified as most prevalent quality goals. Most frequently occurring emotional goals were “involved,” “empowered,” and “informed.”ConclusionThere are alternative methods to face-to-face co-creation seminars, which effectively involve older adults and other stakeholders in the requirements elicitation process. Despite the used elicitation method, the requirements can be easily transformed into goal models to present the results in a uniform way. The common requirements across different pilots provided a strong foundation for representing detailed requirements and input for further software development processes.

Assistive devices could promote independent living and support the active and healthy aging of an older population; however, several factors can badly influence the long-term use of new technologies. In this context, this paper presents a two-step methodology called “pre-validation” that aims to identify the factors that can bias the use of new services, thus minimizing the risk of an unsuccessful longer trial. The proposed pre-validation methodology is composed of two main phases that aim to assess the usability and the reliability of the technology assessed in a laboratory environment and the usability, acceptability, user experience, and reliability of the technology in real environments. The tested services include the socialization scenario, in which older adults are better connected to the community via technological solutions (i.e., socialization applications), and the monitoring scenario, which allows for the introduction of timely interventions (technologies involved include environmental monitoring sensors, a telepresence robot, wearable sensors, and a personalized dashboard). The obtained results underline an acceptable usability level (average System Usability Scale score > 65) for the tested technologies (i.e., socialization applications and a telepresence robot). Phase Two also underlines the good acceptability, user experience, and usability of the tested services. The statistical analysis underlines a correlation between the stress related to the use of technology, digital skills, and intention of use, among other factors. Qualitative feedback also remarks on a correlation between older adults with low digital skills and an anxiety about using technology. Positive correlation indexes were highlighted between the trust and usability scores. Eventually, future long-term trials with assistive technology should rely on motivated caregivers, be founded on a strong recruitment process, and should reassure older adults—especially the ones with low digital literacy—about the use of technology by proposing personalized training and mentoring, if necessary, to increase the trust.

As a consequence of the COVID-19 emergency, frail citizens felt isolated because of social isolation, suspended and/or strongly reduced home assistance, and limited access to hospitals. In this sense, assistive technology could play a pivotal role in empowering frail older adults reducing their isolation, as well as in reinforcing the work of formal caregivers and professionals. In this context, the goal of this paper is to present four pilot studies—conducted from March 2020 to April 2021—to promptly react to COVID-19 by providing assistive technology solutions, aiming to (1) guarantee high-quality service to older adults in-home or in residential facility contexts, (2) promote social inclusion, and (3) reduce the virus transmission. In particular, four services, namely, telepresence service, remote monitoring service, virtual visit, and environmental disinfection, were designed, implemented, and tested in real environments involving 85 end-users to assess the user experience and/or preliminary assess the technical feasibility. The results underlined that all the proposed services were generally accepted by older adults and professionals. Additionally, the results remarked that the use of telepresence robots in private homes and residential facilities increased enjoyment reducing anxiety, whereas the monitoring service supported the clinicians in monitoring the discharged COVID-19 patients. It is also worth mentioning that two new services/products were developed to disinfect the environment and to allow virtual visits within the framework of a hospital information system. The virtual visits service offered the opportunity to expand the portfolio of hospital services. The main barriers were found in education, technology interoperability, and ethical/legal/privacy compliance. It is also worth mentioning the key role played by an appropriate design and customer needs analysis since not all assistive devices were designed for older persons.