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Background Adults with conditions that affect their appearance, known as visible differences, can experience appearance concerns, social anxiety, and depression. Interventions have been developed for this population to facilitate adjustment and coping skills; however, they have limited evidence of efficacy. The Expand Your Horizon [Alleva, J. M., Martijn, C., Van Breukelen, G. J., Jansen, A., & Karos, K. (2015). Expand Your Horizon: A programme that improves body image and reduces self-objectification by training women to focus on body functionality. Body Image, 15, 81–89. https://doi.org/10.1016/j.bodyim.2015.07.001] online functionality-based writing programme was adapted for adults with visible differences.Method A pilot randomised controlled trial with a wait-list control group was carried out to assess preliminary intervention efficacy and gain information about the acceptability and feasibility of the programme. Forty-four adults aged 21–63 years (M = 40.21; SD = 12.05) with visible differences took part. Various facets of body image (i.e. functionality appreciation and body appreciation) as well as depression and anxiety were assessed immediately pre- and post-intervention and at three-months.Results Participants reported enjoying the programme, felt that the format was acceptable, and it significantly increased functionality appreciation, which was maintained at three-months. However, there were no improvements in body appreciation, depression, and anxiety.Conclusions In future, a full trial should be carried out with an active control group.

The COVID-19 pandemic could be a threat for the health status of children with a chronic condition. The present study aimed to explore parents' and children's psychological adjustment during the current pandemic, pursuing a triple objective: to compare the psychological adjustment of parents of children with pediatric rheumatic diseases (PRDs) and parents of healthy children; to analyze children's psychological symptoms (emotional problems and hyperactivity) before and during the COVID-19 pandemic, and with or without a PRDs diagnosis; to explore the associations of children's emotional problems and hyperactivity with parents' psychological adjustment, parent-child interactions and belonging or not to families with PRDs. This cross-sectional study involved 56 parents of children with PRDs and 53 parents of healthy children. Self-report questionnaires about parents' depression, anxiety, parenting stress, and children's emotional symptoms and hyperactivity-inattention were administered. No differences were detected on psychological adjustment between parents of children with PRDs and parents of healthy children. Parents of children with PRDs reported statistically significant higher levels of children's emotional problems and hyperactivity before the pandemic, compared to parents of healthy children; during COVID-19 pandemic, emotional symptoms increased for both groups, while hyperactivity-inattention symptoms increased only in the group of healthy children. Children's emotional difficulties were associated with higher levels of parental anxiety, worse parent-child interaction and having PRDs; children's hyperactivity symptoms were related to parent-child difficult interaction and higher levels of parental depression. Findings suggest the importance to target the children in relation to their parents, when approaching the psychological aspects of PRDs., Author(s): Sonia M. Bramanti [sup.1] , Valerio Manippa [sup.1] [sup.2] , Alessandra Babore [sup.1] , Anna Dilillo [sup.3] , Alessia Marcellino [sup.3] , Vanessa Martucci [sup.3] , Saverio Mallardo [sup.3] [...]

Abstract This study aimed to investigate the effects of combined training (COMB, a combination of moderate-intensity continuous training-MICT and high-intensity interval training-HIIT) vs. continuous MICT administered during a 3-week in-hospital body weight reduction program (BWRP) on body composition, physical capacities, and substrate oxidation in adolescents with obesity. The 3-week in-hospital BWRP entailed moderate energy restriction, nutritional education, psychological counseling, and two different protocols of physical exercise. Twenty-one male adolescents with obesity (mean age: 16.1 ± 1.5 years; mean body mass index [BMI] 37.8 ± 4.5 kg m−2) participated in this randomized control trial study (n:10 for COMB, n:11 MICT), attending ~ 30 training sessions. The COMB group performed 3 repetitions of 2 min at 95% of peak oxygen uptake (V′O2 peak) (e.g., HIIT ≤ 20%), followed by 30 min at 60% of V′O2 peak (e.g., MICT ≥ 80%). Body composition, V′O2 peak, basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate were measured during the first week (W0) and at the end of three weeks of training (W3). The two training programs were equivalent in caloric expenditure. At W3, body mass (BM) and fat mass (FM) decreased significantly in both groups, although the decrease in BM was significantly greater in the MICT group than in the COMB group (BM: − 5.0 ± 1.2 vs. − 8.4 ± 1.5, P

IntroductionThe antigen-presenting cell function of insulin-reactive B cells promotes type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by stimulating pathogenic T cells leading to destruction of insulin-producing β-cells of pancreatic islets.Methods/ResultsTo target insulin-reactive B cells, AKS-107, a human IgG1 Fc molecule fused with human insulin A and B chains, was engineered to retain conformational insulin epitopes that bound mouse and human B cell receptors but prevented binding to the insulin metabolic receptor. AKS-107 Fc-mediated deletion of insulin-reactive B cells was demonstrated via ex vivo and in vivo experiments with insulin-reactive B cell receptor transgenic mouse strains, VH125Tg/NOD and Tg125(H+L)/NOD. As an additional immune tolerance feature, the Y16A mutation of the insulin B(9-23) dominant T cell epitope was engineered into AKS-107 to suppress activation of insulin-specific T cells. In mice and non-human primates, AKS-107 was well-tolerated, non-immunogenic, did not cause hypoglycemia even at high doses, and showed an expectedly protracted pharmacokinetic profile. AKS-107 reproducibly prevented spontaneous diabetes from developing in NOD and VH125Tg/NOD mice that persisted for months after cessation of treatment, demonstrating durable immune tolerance.DiscussionThese preclinical outcomes position AKS-107 for clinical development in T1D prevention settings.

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.

Antithrombotic therapies (ATT) play a pivotal role in the management of cardiovascular diseases, aiming to prevent ischemic events while maintaining a delicate balance with the patient’s bleeding risk. Typically, ATT can be classified into antiplatelet and anticoagulant therapies. Their application spans a broad spectrum of cardiovascular conditions, ranging from ischemic heart disease to atrial fibrillation, encompassing venous thromboembolisms and innovative structural interventional cardiology procedures. The global burden of cardiovascular diseases is steadily increasing, often giving rise to overlapping clinical presentations. Accordingly, the adoption of combined pharmacological approaches becomes imperative, potentially disrupting the delicate equilibrium between ischemic and bleeding risk, thus leading to nuanced pharmacotherapeutic pathways. In this context, contemporary investigations strive to identify a convergence point that optimizes the duration of medical therapy while addressing the need for antithrombotic effects, especially in the context of ischemic heart disease. This review aims to comprehensively revisit the main antithrombotic strategies in cardiovascular diseases, with the intention of enhancing a systematic approach which is key for the effective clinical management of these patients. Also, the review will examine the most impactful studies that have established the groundwork for current scientific evidence, with acknowledgement of special populations. Finally, we will cast a gaze into the future of this dynamic and evolving research field, exploring forthcoming perspectives and advancements.

Background/Objectives: A weekly combination of a high volume of moderate-intensity continuous training (MICT) with a low volume of high-intensity interval training (HIIT) provides important improvements in body composition and physical capacities in individuals with obesity. However, previous studies did not determine the weekly proportions of HIIT and MICT a priori. This study aimed to investigate changes in body composition, physical capacities and the fat oxidation rate in obese male adults by comparing a combination of MICT and HIIT, called combined training (COMB), with HIIT for a 12-week period. Methods: Thirty-four obese male adults (mean age: 39.4 ± 7.0 y; mean body mass index [BMI] 34.0 ± 4.2 kg·m−2) participated in this study (n = 18 for COMB, n = 16 HIIT), attending ∼ 36 training sessions. The COMB group performed 3 repetitions of 2 min at 95% of peak oxygen uptake (V’O2 peak) (e.g., HIIT ≤20%), followed by 30 min at 60% of VO2 peak (e.g., MICT ≥80%). The HIIT group performed 5–7 repetitions of 2 min at 95% of VO2 peak. At baseline (PRE) and at the end of the training period (POST), body composition, VO2 peak, and the fat oxidation rate were measured. The two training programs were equivalent in caloric expenditure. Results: At POST, body mass (BM) and fat mass (FM) decreased by a mean of 3.09 ± 3.21 kg and 3.90 ± 2.40 kg, respectively (P

BackgroundIn the last decade a large number of studies proposed and/or validated equations to estimate the Resting Energy Expenditure (REE) in adults and/or older adults, however, no equation currently available showed good accuracy for older adults with severe obesity. Thus, this study aimed to develop and validate new predictive equations for REE, based on data from the indirect calorimetry, in Italian older adults with severe obesity.MethodsA retrospective study was as conducted with 764 Caucasian older adults with severe obesity (age range: 60-74 years and BMI ≥ 35 kg/m/²). Four models were used to test the accuracy of anthropometry and body composition variables in multivariable prediction of REE. All models were derived by stepwise multiple regression analysis using a calibration group of 382 subjects [295 females and 87 males] and the equations were cross-validated in the remaining 382 subjects [295 females and 87 males] as validation group. The new prediction equations and the other published equations were tested using the Bland-Altman method. Prediction accuracy was defined as the percentage of subjects whose REE was predicted within ± 10% of measured REE.ResultsAll the equations analyzed predicted higher energy requirements for males than females, and most of them underestimated the energy requirement values of our sample. The highest accuracy values were observed in the new equations, with 62% in the anthropometric model and 63% in the body composition model.ConclusionAlthough the accuracy of our equations was slightly higher in comparison with the other taken into consideration, they cannot be considered completely satisfactory for predicting REE in Italians older adults with severe obesity. When predicting equations cannot guarantee precise or acceptable values of REE, the use of indirect calorimetry (if available) should be always recommended, especially in clinical practice.

BackgroundThe increasing use of smartphones, wearables, and connected devices has enabled the increasing application of digital technologies for research. Remote digital study platforms comprise a patient-interfacing digital application that enables multimodal data collection from a mobile app and connected sources. They offer an opportunity to recruit at scale, acquire data longitudinally at a high frequency, and engage study participants at any time of the day in any place. Few published descriptions of centralized digital research platforms provide a framework for their development. ObjectiveThis study aims to serve as a road map for those seeking to develop a centralized digital research platform. We describe the technical and functional aspects of the ehive app, the centralized digital research platform of the Hasso Plattner Institute for Digital Health at Mount Sinai Hospital, New York, New York. We then provide information about ongoing studies hosted on ehive, including usership statistics and data infrastructure. Finally, we discuss our experience with ehive in the broader context of the current landscape of digital health research platforms. MethodsThe ehive app is a multifaceted and patient-facing central digital research platform that permits the collection of e-consent for digital health studies. An overview of its development, its e-consent process, and the tools it uses for participant recruitment and retention are provided. Data integration with the platform and the infrastructure supporting its operations are discussed; furthermore, a description of its participant- and researcher-facing dashboard interfaces and the e-consent architecture is provided. ResultsThe ehive platform was launched in 2020 and has successfully hosted 8 studies, namely 6 observational studies and 2 clinical trials. Approximately 1484 participants downloaded the app across 36 states in the United States. The use of recruitment methods such as bulk messaging through the EPIC electronic health records and standard email portals enables broad recruitment. Light-touch engagement methods, used in an automated fashion through the platform, maintain high degrees of engagement and retention. The ehive platform demonstrates the successful deployment of a central digital research platform that can be modified across study designs. ConclusionsCentralized digital research platforms such as ehive provide a novel tool that allows investigators to expand their research beyond their institution, engage in large-scale longitudinal studies, and combine multimodal data streams. The ehive platform serves as a model for groups seeking to develop similar digital health research programs. International Registered Report Identifier (IRRID)DERR1-10.2196/49204

no Abstract

In mammals, glucose transporters (GLUT) control organism-wide blood-glucose homeostasis. In human, this is accomplished by 14 different GLUT isoforms, that transport glucose and other monosaccharides with varying substrate preferences and kinetics. Nevertheless, there is little difference between the sugar-coordinating residues in the GLUT proteins and even the malarial Plasmodium falciparum transporter PfHT1, which is uniquely able to transport a wide range of different sugars. PfHT1 was captured in an intermediate ‘occluded’ state, revealing how the extracellular gating helix TM7b has moved to break and occlude the sugar-binding site. Sequence difference and kinetics indicated that the TM7b gating helix dynamics and interactions likely evolved to enable substrate promiscuity in PfHT1, rather than the sugar-binding site itself. It was unclear, however, if the TM7b structural transitions observed in PfHT1 would be similar in the other GLUT proteins. Here, using enhanced sampling molecular dynamics simulations, we show that the fructose transporter GLUT5 spontaneously transitions through an occluded state that closely resembles PfHT1. The coordination of D-fructose lowers the energetic barriers between the outward- and inward-facing states, and the observed binding mode for D-fructose is consistent with biochemical analysis. Rather than a substrate-binding site that achieves strict specificity by having a high affinity for the substrate, we conclude GLUT proteins have allosterically coupled sugar binding with an extracellular gate that forms the high-affinity transition-state instead. This substrate-coupling pathway presumably enables the catalysis of fast sugar flux at physiological relevant blood-glucose concentrations.

Sugar porters (SPs) represent the largest group of secondary-active transporters. Some members, such as the glucose transporters (GLUTs), are well known for their role in maintaining blood glucose homeostasis in mammals, with their expression upregulated in many types of cancers. Because only a few sugar porter structures have been determined, mechanistic models have been constructed by piecing together structural states of distantly related proteins. Current GLUT transport models are predominantly descriptive and oversimplified. Here, we have combined coevolution analysis and comparative modeling, to predict structures of the entire sugar porter superfamily in each state of the transport cycle. We have analyzed the state-specific contacts inferred from coevolving residue pairs and shown how this information can be used to rapidly generate free-energy landscapes consistent with experimental estimates, as illustrated here for the mammalian fructose transporter GLUT5. By comparing many different sugar porter models and scrutinizing their sequence, we have been able to define the molecular determinants of the transport cycle, which are conserved throughout the sugar porter superfamily. We have also been able to highlight differences leading to the emergence of proton-coupling, validating, and extending the previously proposed latch mechanism. Our computational approach is transferable to any transporter, and to other protein families in general.

Background: Adults with conditions that affect their appearance, known as visible differences, can experience appearance concerns, social anxiety, and depression. Interventions have been developed for this population to facilitate adjustment and coping skills; however, they have limited evidence of efficacy. The Expand Your Horizon [Alleva, J. M., Martijn, C., Van Breukelen, G. J., Jansen, A., & Karos, K. (2015). Expand Your Horizon: A programme that improves body image and reduces self-objectification by training women to focus on body functionality. Body Image, 15, 81–89. ] online functionality-based writing programme was adapted for adults with visible differences. Method: A pilot randomised controlled trial with a wait-list control group was carried out to assess preliminary intervention efficacy and gain information about the acceptability and feasibility of the programme. Forty-four adults aged 21–63 years (M = 40.21; SD = 12.05) with visible differences took part. Various facets of body image (i.e. functionality appreciation and body appreciation) as well as depression and anxiety were assessed immediately pre- and post-intervention and at three-months. Results: Participants reported enjoying the programme, felt that the format was acceptable, and it significantly increased functionality appreciation, which was maintained at three-months. However, there were no improvements in body appreciation, depression, and anxiety. Conclusions: In future, a full trial should be carried out with an active control group. [ABSTRACT FROM AUTHOR]