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    Reporting medical device-related pressure ulcers: An international Delphi consensus study

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    Background: Pressure ulcers that are caused from the application of medical devices for diagnostic or therapeutic purposes are commonly observed in acute care environments. Despite an improved understanding of the factors causing these wounds, there is no current consensus on reporting. Objective: To develop an international consensus for reporting medical device related pressure ulcers. Design: A modified RAND/UCLA Delphi study. Settings: International experts from clinical, academic and industrial stakeholder. Participants: 95 international clinicians and tissue viability experts. Methods: A Delphi survey was developed through literature review and qualitative synthesis. It was electronically disseminated through gate keepers to international experts in the field, with three rounds of consensus feedback. Median values and Disagreement Index from Likert scales were used to establish consensus. Results: The panel achieved consensus for reporting MDRPUs which included 30 items across 5 Themes which included i) Recording medical device care, ii) Reporting medical device-related pressure ulcer, iii) Device specific reporting, iv) Ulcer reporting and v) patient information. Conclusions: This is the first international study to develop consensus on medical device related pressure ulcer reporting. This could be used to support standardised international reporting to improve care standards. Tweetable abstract: This international Delphi consensus study established a core reporting data set for medical device related pressure ulcers. This study will inform the design of future reporting tools to support standardised practice.e.g. Tweetable abstract: international consensus on medical device related pressure injury monitoring @EPUAP @NPIAP @SkinSensing

    Difference in adverse neonatal outcomes between preterm singletons and twins possibly explained by placental abnormalities

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    Introduction: The purpose of this study was to compare microscopic placental characteristics between preterm twins and singletons, and between preterm monochorionic and dichorionic twins, in order to explore the effect of placental pathology on adverse neonatal outcomes. Methods: This study included 566 neonates born ≤32 weeks and/or ≤1500 g, of whom 429 were singletons and 137 were twins (38 monochorionic and 99 dichorionic). Clinical data was retrospectively collected, and placentas were prospectively examined for maternal vascular malperfusion, fetal vascular malperfusion and placental inflammation (acute and chronic). Results: Singletons had increased rates of maternal vascular malperfusion, fetal hypoxia, funisitis (in umbilical cord and chorial plate), chronic deciduitis, and villitis of unknown etiology compared to twins. Delayed villous maturation and ischemia were more frequently present in monochorionic placentas than in dichorionic. Singletons had a significant lower birthweight and were more often small for gestational age than twins. Multivariate linear regression analysis adjusting for singleton pregnancy, gestational hypertension and placental abnormalities showed that gestational hypertension (β = −114.8), infarct (β = −130.1), decidual necrosis (β = −115.4), fetal hypoxia (β = −59.3) and chronic deciduitis (β = −118.8) were independently associated with lower birthweight. Multivariate regression analysis revealed five independent risk factors of small for gestational age: gestational hypertension (OR 4.4), infarct (OR 3.7), decidual necrosis (OR 2.7), fetal hypoxia (OR 1.9) and villitis (OR 5.2). Discussion: Singleton pregnancies vary in histological placental abnormality rates from twin pregnancies. This study demonstrated that differences in birthweight and small for gestational age rates between preterm twins and singletons can be attributed to gestational hypertension and histological placental abnormalities

    Development of Reliable and High-Throughput Human Biomimetic Cartilage and Bone Models to Explore Senescence and Personalized Osteoarthritis Treatment Options

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    To facilitate effective preclinical testing of senescence treatments for osteoarthritis (OA), we have created reliable biomimetic and high-throughput models using aged human joint tissues. Moreover, concerns regarding scalability led to the concurrent development of a high-throughput human in vitro senescence cartilage organoid model. Osteochondral explants and cells for the cartilage organoid model were isolated from patients undergoing joint replacement surgery due to OA. To induce senescence, explants and organoids were subjected to radiation and/or mechanical loading. Samples were harvested; gene expression of relevant senescent and cartilage genes was measured using RT-qPCR, and protein expression was evaluated using histology. A general senescence phenotype was induced by the perturbations, as shown by senescence-associated β-galactosidase staining. In-depth gene expression analysis revealed that hyperphysiological mechanical loading upregulated gene expression of IL8 and SERPINE1, representing aspects of a senescence-associated secretory phenotype (SASP) profile. Irradiation upregulated CDKN1A, encoding p21, and downregulated LMNB1, representing a cell cycle arrest profile with the absence of a SASP response. Combining the two perturbations showed upregulation of CDKN1A, IL8, and SERPINE and downregulation of LMNB1, representing a complementary senescence model. The high-throughput human in vitro cartilage organoid senescence model showed similar effects to the irradiation explant model. In this study, we present a variety of senescence models of human aged chondrocytes that allows for rapid initial screening of anti-senescence compounds in high-throughput, as well as in-depth, characterization of post-mitotic aged chondrocytes prone to OA pathophysiology. This research advances the development of essential therapeutics for OA

    Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life

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    Most therapeutic antibodies are based on immunoglobulin G (IgG) due to their potent effector functions and long plasma half-life. However, also monomeric IgA has emerged as an attractive candidate for cancer treatment as, upon specific binding to tumor cells, it can activate myeloid cells, like polymorphonuclear leukocytes and macrophages, to kill the tumor cells by engaging the Fc α receptor I (FcαRI). Despite this favorable property, human IgA has a short plasma half-life in both mice and humans, which is clearly limiting preclinical studies in a translational perspective. Here, we report on albumin-equipped designs of human IgA antibodies that are long acting due to tailored binding to the human form of neonatal Fc receptor (FcRn), which is a natural plasma half-life regulator of albumin. Importantly, this was achieved without compromising the ability of IgA to engage and activate FcαRI-expressing effector cells for tumor cell killing in vitro and in vivo in a new mouse model transgenic for the human forms of FcRn and FcαRI. We further show that the potency of the engineered long-acting human IgA against tumor cells with intermediate target antigen expression levels could be enhanced by myeloid checkpoint inhibitors targeting the signal regulatory protein α-CD47 axis

    The Role of Environmental Factors in Technology-Assisted Physical Activity Intervention Studies Among Older Adults: Scoping Review

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    BACKGROUND: The rapidly emerging integration of both technological applications and environmental factors in physical activity (PA) interventions among older adults highlights the need for an overarching investigation. OBJECTIVE: This scoping review compiled the current literature and aimed to provide an overview of the role of physical, social, socioeconomic, and systemic environmental factors in technology-assisted PA interventions for older adults. METHODS: We systematically searched 6 common databases up to September 16, 2024, for original longitudinal studies (with at least one preintervention measurement and one postintervention measurement) that reported on the role of environmental factors in technology-assisted PA interventions for independently living, community-dwelling older adults. In a stepwise process, data on study characteristics (step 1), environmental factors and their role in the included studies (step 2), and intervention outcomes and effects by type of environmental factor (step 3) were summarized. RESULTS: A total of 8020 articles were screened, and 25 (0.31%) were included. Most studies were conducted in Europe (11/25, 44%), followed by North America (5/25, 20%), Asia (5/25, 20%), and Oceania (4/25, 16%). Social environmental factors were most often considered (19/25, 76%), followed by factors from the physical (8/25, 32%), socioeconomic (1/25, 4%), and systemic environment (1/25, 4%). Environmental factors were used as the outcome (8/25, 32%), setting variable (7/25, 28%), moderator or facilitator (8/25, 32%), and intervention component (3/25, 12%). In most studies (19/25, 76%), the intervention had a beneficial effect on the outcome of interest, and the included environmental factor played a supportive role in achieving this effect. In some studies, no effect (3/25, 12%), mixed effects (2/25, 8%), or adverse effects (1/25, 4%) of the interventions were reported. CONCLUSIONS: This is the first comprehensive description of how environmental factors interact with technology-assisted interventions to increase or optimize PA in older adults. It was found that the investigation of environmental factors in this field is at an early stage. Environmental factors were found to play a supportive role in achieving beneficial effects of technology-assisted PA interventions, but the findings were based on a heterogeneous empirical platform. Still, certain aspects such as the application of virtual reality environments and social (or peer) comparison have shown significant potential that remains to be leveraged. A better understanding of intervention results and support in tailoring intervention programs can be provided through the inclusion of environmental aspects in technology-assisted PA interventions for older adults

    Unveiling the Dynamics of SARS-CoV-2 Gamma and Delta Waves in Paraná, Brazil – Delta Displacing a Persistent Gamma Through Alternative Routes of Dispersal

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    The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs

    Symptom networks of psychotic experiences and functional somatic symptoms in adolescence: A cross-sectional study of two population-based cohorts

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    Background: Contemporary theoretical models underlying development of psychotic- and functional disorders show similarities, including attribution of aberrant salience to everyday (bodily) sensations and an increased tendency of top-down generation of perception. In two general population samples of adolescents, we aimed to examine potential associations between subclinical phenomena, namely functional somatic symptoms (FSS) and psychotic experiences (PE). Methods: We used data from two cohorts of adolescents aged 15–17 years: the Copenhagen Child Cohort 2000 (Denmark, n = 2550) and the TRacking Adolescents' Individual Lives Survey (the Netherlands, n = 1665). We identified comparable self-reported symptoms of FSS and PE respectively in each cohort. The cohort data were analyzed separately to enable replication, and mixed graphical models were used to estimate symptom networks. First, networks including only FSS and PE were modelled. Second, an emotional symptom score was included in the networks. Results: While numerous specific symptom-to-symptom cross-domain associations were not replicated, symptom networks of the two cohorts overall showed relatively comparable patterns. Delusions of persecution showed the strongest connection with FSS in both cohorts. In the models including emotional symptoms, emotional problems were associated with many PE and FSS, but did not fundamentally change the structure of the original networks. Conclusion: Using a symptom-based approach the current study lent little support to the notion of specific associations between PE and FSS, yet associations between FSS and PE in adolescence were found in both cohorts. The associations between the two domains could not be fully explained by shared associations with emotional problems

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    Aortic, musculoskeletal and organ characteristics on computed tomography in knee osteoarthritis - an explorative study in the IMI-APPROACH cohort

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    The systemic associations with knee osteoarthritis (KOA) are incompletely understood. This study explores aortic disease, musculoskeletal and organ findings in patients with KOA in relation to their symptoms or radiographic abnormalities. Full body computed tomography (CT) scans of 255 IMI-APPROACH participants were investigated using an automated analysis of multislice CT (Voronoi Health Analytics) that extracts aortic size and calcifications, and volumes and densities of bones, muscles, fat compartments and thoracic and abdominal organs. The CT measurements were primarily related to KOA as measured with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual scores and automated knee radiograph analysis of osteophytes, bone sclerosis and joint space width. The median age was 67 years, body mass index (BMI) 26.8 kg/m2 and 78% were female. About half had Kellgren-Lawrence grade ≥ 2. Larger knee osteophyte area was associated with a larger aortic volume (RSpearman=0.21,P = 0.001), which can be due to elongation or dilatation. We observed an association between more symptoms and increased psoas (RSpearman=-0.23,P < 0.001) and lower leg (RSpearman=-0.23,P < 0.001) muscle density, suggesting less microscopic muscle fat. Symptomatic KOA was associated with substantially lower lung volume (771 ml difference between 50% worst and 50% best WOMAC), but not with visible lung disease. Lung volume and density were significantly associated with the physical functioning WOMAC component. These associations remained significant after adjustment for age, sex and BMI. KOA is associated with significant systemic changes, including altered aortic and organ volumes. These correlations suggest that KOA’s impact may extend beyond the joints. Future research should explore the causal relationships and therapeutic implications associations

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