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Sergio Cinocca,1 Paola Rucci,1 Concetta Randazzo,1 Elizabeth Teale,2 Davide Pianori,1 Emanuele Ciotti,3 Maria Pia Fantini1 1Department of Biomedical and Neuromotor Sciences, Unit of Hygiene, Public Health and Biostatistics, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 2Academic Unit of Elderly Care and Rehabilitation, Bradford Institute for Health Research, Bradford, UK; 3Bologna Local Health Authority, Bologna, Italy Background: Intermediate care (IC) services are a key component of integrated care for elderly people, providing a link between hospital and home through provision of rehabilitation and health and social care. The Patient Reported Experience Measures (PREMs) are designed to measure user experience of care in IC settings. Objective: To examine the feasibility and the scaling properties of the Italian version of PREMs questionnaires for use in IC services.Methods: A cross-sectional survey was conducted on consecutive users of 1 home-based and 4 bed-based IC services in Emilia-Romagna (Italy). The main outcome measure was the PREMs questionnaire results. PREMs for each home- and bed-based IC services were translated, back-translated, and adapted through consensus among the members of the advisory board and pilot testing of face validity in 15 patients. A total of 199 questionnaires were returned from users of bed-based services and 185 were returned by mail from users of home-based services. The return rates and responses were examined. Mokken analysis was used to examine the scaling properties of the PREMs.Results: Analysis performed on the bed-based PREMs (N=154) revealed that 13 items measured the same construct and formed a moderate-strength scale (Loevinger H=0.488) with good reliability (Cronbach’s alpha =0.843). Analysis of home-based PREMs (N=134 records) revealed that 15 items constituted a strong scale (Loevinger H=0.543) with good reliability (Cronbach’s alpha =0.875).Conclusion: The Italian versions of the bed- and home-based IC-PREMs questionnaires proved to be valid and reliable tools to assess patients’ experience of care. Future plans include monitoring user experience over time in the same facilities and in other Italian IC settings for between-service benchmarking. Keywords: intermediate care, patient-reported experience measures, validation, elderly

Abstract Background Skeletal Stem Cells (SSCs) are required for skeletal development, homeostasis, and repair. The perspective of their wide application in regenerative medicine approaches has supported research in this field, even though so far results in the clinic have not reached expectations, possibly due also to partial knowledge of intrinsic, potentially actionable SSC regulatory factors. Among them, the pleiotropic cytokine RANKL, with essential roles also in bone biology, is a candidate deserving deep investigation. Methods To dissect the role of the RANKL cytokine in SSC biology, we performed ex vivo characterization of SSCs and downstream progenitors (SSPCs) in mice lacking Rankl (Rankl −/− ) by means of cytofluorimetric sorting and analysis of SSC populations from different skeletal compartments, gene expression analysis, and in vitro osteogenic differentiation. In addition, we assessed the effect of the pharmacological treatment with the anti-RANKL blocking antibody Denosumab (approved for therapy in patients with pathological bone loss) on the osteogenic potential of bone marrow-derived stromal cells from human healthy subjects (hBMSCs). Results We found that, regardless of the ossification type of bone, osteochondral SSCs had a higher frequency and impaired differentiation along the osteochondrogenic lineage in Rankl −/− mice as compared to wild-type. Rankl −/− mice also had increased frequency of committed osteochondrogenic and adipogenic progenitor cells deriving from perivascular SSCs. These changes were not due to the peculiar bone phenotype of increased density caused by lack of osteoclast resorption (defined osteopetrosis); indeed, they were not found in another osteopetrotic mouse model, i.e., the oc/oc mouse, and were therefore not due to osteopetrosis per se. In addition, Rankl −/− SSCs and primary osteoblasts showed reduced mineralization capacity. Of note, hBMSCs treated in vitro with Denosumab had reduced osteogenic capacity compared to control cultures. Conclusions We provide for the first time the characterization of SSPCs from mouse models of severe recessive osteopetrosis. We demonstrate that Rankl genetic deficiency in murine SSCs and functional blockade in hBMSCs reduce their osteogenic potential. Therefore, we propose that RANKL is an important regulatory factor of SSC features with translational relevance.

Fixation constraints in visual tasks are ubiquitous in visual and cognitive neuroscience. Despite its widespread use, fixation requires trained subjects, is limited by the accuracy of fixational eye movements, and ignores the role of eye movements in shaping visual input. To overcome these limitations, we developed a suite of hardware and software tools to study vision during natural behavior in untrained subjects. We measured visual receptive fields and tuning properties from multiple cortical areas of marmoset monkeys who freely viewed full-field noise stimuli. The resulting receptive fields and tuning curves from primary visual cortex (V1) and area MT match reported selectivity from the literature which was measured using conventional approaches. We then combined free viewing with high-resolution eye tracking to make the first detailed 2D spatiotemporal measurements of foveal receptive fields in V1. These findings demonstrate the power of free viewing to characterize neural responses in untrained animals while simultaneously studying the dynamics of natural behavior.

Background: The concept of unfinished nursing care (UNC) describes nursing interventions required by patients and families that nurses postpone or omit. UNC reasons have been documented; however, no studies have summarised the underlying factors triggering the UNC during the pandemic. Therefore, the aim was to synthesise the available studies exploring factors affecting UNC during a pandemic. Methods: We conducted an integrative review following Whittemore and Knafl’s framework according to the Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Scopus databases were searched for primary studies that collected data from 1 January 2020 to 1 May 2023. Both qualitative and quantitative studies assessing the reasons for UNC were eligible and evaluated in their quality using the Critical Appraisal Skills Programme and the Mixed Methods Appraisal Tool. Results: Four studies were included—three qualitative and one cross-sectional. The reasons for UNC have been documented at the following levels: (a) system (e.g., new healthcare system priorities); (b) unit (e.g., ineffective work processes); (c) nurse management (e.g., inadequate nurse manager’s leadership); (d) nurse (e.g., nurses’ attitudes, competences, performances); and (e) patient (increased demand for care). Conclusion: The reasons for UNC during the COVID-19 pandemic are different to those documented in the pre-pandemic times and reflect a pre-existing frailty of the National Health Service towards nursing care.

Background: Out-of-hospital cardiac arrest (OHCA) is a major health concern in Europe, leading to significant morbidity and mortality. Survivors often suffer from cognitive deficits, anxiety, and depression, that affect significantly their quality of life. Current post-discharge care is inconsistent and frequently overlooks subtle but disabling symptoms. The ENFORCER trial aims to significantly enhance the health and quality of life of OHCA survivors by providing a comprehensive, accessible, and user-friendly internet-based lifestyle intervention. Methods: ENFORCER is a multicentre, parallel group randomized controlled trial involving OHCA survivors aged 18–80 years with cognitive impairment or anxiety/depression measured through validated instruments.Participants will be randomized 1:1 to the intervention or the control group. The intervention group will receive a one-year program via a secure web application, offering cognitive, emotional, and physical rehabilitation support. The control group will receive standard care.The primary outcome is the difference in the proportion of patients without cognitive or emotional symptoms between the two groups after one year.Secondary outcomes include changes in the level of patients’ cognitive and emotional symptoms, quality of life, sleep quality, sexual interest and satisfaction, and caregivers’ burden, quality of life, sleep quality and emotional symptoms in the two groups. Discussion: The trial addresses the need for consistent post-discharge care, and the timely detection and treatment of cognitive and emotional problems. The internet-based approach allows to potentially reach many patients, ensuring cost-effectiveness and high adherence rates.The study results could establish a standard for post-OHCA care, improving long-term recovery and quality of life for survivors.Trial registration.The trial is registered at clinicaltrials.gov (NCT06395558).

Physical activity is essential to a healthy lifestyle for adults with spinal cord injuries (SCI). Although exercise is recognised as an important tool for improving the well-being and independence of people with SCI, most individuals do not engage in physical exercise. Traditional exercise programmes often require participation in rehabilitation centres or specialised facilities, making them less accessible for individuals with chronic SCI. Many people with SCI live in rural communities and other geographically isolated areas where access to fitness facilities and outdoor recreational areas involves long commutes or expensive transportation, which is one of the most common barriers to exercise reported by people with physical disabilities. Consequently, exercise remains an underused intervention for improving health and function in people with SCI despite its proven effects in reducing pain, fatigue, fall risk and other secondary health conditions. This pilot study evaluates the feasibility and acceptability of a home-based supervised exercise programme for individuals with chronic SCI. The study will be an interventional and prospective pilot study. People with SCI will participate in a 3-month home-based exercise programme. Primary outcomes will include adherence to the exercise programme, while secondary outcomes will encompass quality of life, functional capacity, musculoskeletal health and clinical parameters. The programme will be structured into 1-hour sessions, held twice weekly for 3 months, conducted online and in small groups. The results of this study could be relevant for future indications of the best setting and strategy to ensure adherence to physical activity.

IMPORTANCE:. The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES:. To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES:. We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS:. We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3–11%) and 39% (95% CI, 28–49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129–1341 µg) in the KPNC cohort and 200 µg (IQR, 0–1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1–7%) and 20% (95% CI, 15–26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE:. In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals’ analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

Abstract St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) are arboviruses transmitted by Culex mosquitoes and amplified in avian hosts. The present study aimed to investigate the presence and seasonal circulation of SLEV and WNV in La Rioja province, within the semiarid ecoregion of the Monte, Argentina. Over a two-year period, avian sera were collected and tested for neutralizing antibodies against SLEV and WNV. Our results reveal the enzootic activity of both viruses in this challenging environment. SLEV seroprevalence was 4.5% (35/778), with higher activity in spring (2016) and autumn (2017). WNV seroprevalence was 3.5% (27/778), peaking during the summer 2016–2017. Greater seroprevalence for SLEV in 2016 was detected for the Lark-like Brushrunner (Coryphistera alaudina) and the Short-billed Canastero (Asthenes baeri) and in 2017 for the Black-crested Finch (Lophospingus pusillus) and Lark-like Brushrunner, whereas for WNV greater seroprevalence in 2016 was detected for the Picui Ground Dove (Columbina picui) and in 2017 for the Lark-like Brushrunner and Band-tailed Seedeater (Catamenia analis). Additionally, five avian individuals experienced seroconversion during the sampling period, namely the Lark-like Brushrunner and White-fronted Woodpecker (Melanerpes cactorum) for SLEV, and the Lark-like Brushrunner, Greater Wagtail Tyrant (Stigmatura budytoides) and Many-colored Chaco Finch (Saltatricula multicolor) for WNV. The study highlights the persistence and circulation of these viruses in a semiarid ecosystem, raising questions about overwintering mechanisms and transmission dynamics. This research contributes to understanding arbovirus ecology in diverse environments. Further investigations are needed to assess the specific mechanisms facilitating virus persistence in the Monte ecoregion.

Medicinal plants have been explored worldwide as potential alternatives for the prevention and treatment of different diseases, including viral infections. Baccharis crispa Spreng. (Asteraceae) is a native medicinal species widely used in South America. Given the influence of genetic and environmental factors on secondary metabolites biosynthesis and accumulation, this study aimed to evaluate the in vitro antiviral activity of four wild populations of B. crispa from Córdoba, Argentina, and assess the variability in their bioactivity and chemical composition. The cytotoxicity of chloroform, ethanol, and aqueous extracts from aerial parts was evaluated by the neutral red uptake method. Antiviral and virucidal activity against herpes simplex virus type 1 (HSV-1) and chikungunya virus (CHIKV) were assessed via plaque-forming unit (PFU) reduction assay. Phytochemical analyses of the extracts were conducted using HPLC-ESI- MS/MS. The Puesto Pedernera population showed the strongest antiviral activity, with inhibition rates of 82% for CHIKV and 79% against HSV-1, as well as potent virucidal effects, reducing PFU formation by up to 5 logarithms for both viruses. Remarkably, ethanol extract exhibited the least toxicity and strongest inhibitory activity. Villa del Parque population was inactive. We identified 38 secondary metabolites, predominantly phenolic acids (12) and flavonoids (18), in varying proportions. Delphinidin and delphinidin-3-glucoside are described for the first time in the species. Differences in phytochemical profiles were observed among extract types and populations. Key phenolic compounds showed moderate positive correlations with the evaluated bioactivities, emphasizing the complexity of phytochemical properties and interactions. These results highlight the therapeutic potential of B. crispa extracts against viral infections and underscore the importance of considering the geographical source of plant material in bioactivity evaluations.

Accurate precipitation measurement is critical for managing flood and drought risks. Traditional meteorological tools, such as rain gauges and remote sensors, have limitations in resolution, coverage, and cost-effectiveness. Recently, the opportunistic use of microwave communication signals has been explored to improve precipitation estimation. While there is growing interest in using satellite-to-earth microwave links (SMLs) for machine learning-based precipitation estimation, direct rainfall estimation from raw signal-to-noise ratio (SNR) data via deep learning remains underexplored. This study investigates a range of machine learning (ML) approaches, including deep learning (DL) models and traditional methods like gradient boosting machine (GBM), for estimating rainfall rates from SNR data collected by interactive satellite receivers. We develop real-time models for rainfall detection and estimation using downlink SNR signals from satellites to user terminals. By leveraging a year-long dataset from multiple locations—including SNR measurements paired with disdrometer and rain-gauge data—we explore and evaluate various ML models. Our final models include ensemble approaches for both rainfall detection and cumulative rainfall estimation. The proposed models provide a reliable solution for estimating precipitation using Earth–satellite microwave links, potentially improving precipitation monitoring. Compared to the state-of-the-art power-law-based models applied to similar datasets reported in the literature, our ML models achieve a 46% reduction in the root mean squared error (RMSE) for event-based cumulative precipitation predictions.

Background:. Spasticity is a serious complication of spinal cord injury/disease (SCI/D) that affects 60%–80% of patients with this condition. The presence of spasticity can have a significant impact on the outcomes of reconstructive surgical interventions, such as those on pressure sores (PSs). Moreover, in the conservative treatment of PSs, spasticity may prevent maintaining adequate postures to avoid skin friction or traction. The aim of this study is to describe the PS reconstruction outcomes in a cohort of patients with SCI/D affected by spasticity. Methods:. In this retrospective study of patients with SCI/D consecutively admitted to Montecatone Rehabilitation Institute between October 2013 and March 2022, 54 PSs were treated in 46 people with spasticity. Results:. Postsurgery complications occurred in 26 of 54 treated PS, of which seven were major. Eleven patients experienced more than one complication. The overall incidence of postsurgical complications was 48.1%, and the incidence of major complications was 13%. Median length of hospital stay was 3.8 versus 1.8 months. Compared with other reports in the literature of PS reconstruction in patients with SCI/D, we found higher rates of overall, minor, and major complications. Conclusions:. Spasticity proved to be an important condition to consider, and its treatment requires specialized physicians. The collaboration between plastic surgeons and spasticity specialists is crucial to define the best treatment to reduce postoperative complications.

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA on inflammation, paracellular permeability, epigenetics and mitochondrial functions. The expression levels of pro-inflammatory cytokines (IL-6, IL-1β) increased significantly after 24 h exposure to TMA 1 mM. TMA exposure was associated with an upregulation of SIRT1 (TMA 1 mM, 400 μM, 10 μM) and DNMT1 (TMA 1 mM, 400 µM) genes, while DNMT3A expression decreased (TMA 1 mM). In a cell-free model, TMA (from 0.1 µM to 1 mM) induced a dose-dependent reduction in Sirtuin enzyme activity. In Caco-2 cells, TMA reduced total ATP levels and significantly downregulated ND6 expression (TMA 1 mM). TMA excess (1 mM) reduced intracellular mitochondrial DNA copy numbers and increased the methylation of the light-strand promoter in the D-loop area of mtDNA. Also, TMA (1 mM, 400 µM, 10 µM) increased the permeability of Caco-2 epithelium, as evidenced by the reduced transepithelial electrical resistance values. Based on our preliminary results, TMA excess might promote inflammation in intestinal cells and disturb epigenetic and mitochondrial homeostasis.

Abstract Fixation constraints in visual tasks are ubiquitous in visual and cognitive neuroscience. Despite its widespread use, fixation requires trained subjects, is limited by the accuracy of fixational eye movements, and ignores the role of eye movements in shaping visual input. To overcome these limitations, we developed a suite of hardware and software tools to study vision during natural behavior in untrained subjects. We measured visual receptive fields and tuning properties from multiple cortical areas of marmoset monkeys who freely viewed full-field noise stimuli. The resulting receptive fields and tuning curves from primary visual cortex (V1) and area MT match reported selectivity from the literature which was measured using conventional approaches. We then combined free viewing with high-resolution eye tracking to make the first detailed 2D spatiotemporal measurements of foveal receptive fields in V1. These findings demonstrate the power of free viewing to characterize neural responses in untrained animals while simultaneously studying the dynamics of natural behavior.

Abstract Background Patient-reported outcome measures (PROMs) are increasingly being used to assess the effectiveness of elective total knee arthroplasty (TKA). However, little is known about how PROMs scores change over time in these patients. The aim of this study was to identify the trajectories of quality of life and joint functioning, and their associated demographic and clinical features in patients undergoing elective TKA. Methods A prospective, cohort study was conducted, in which PROMs questionnaires (Euro Quality 5 Dimensions 3L, EQ-5D-3L, and Knee injury and Osteoarthritis Outcome Score Patient Satisfaction, KOOS-PS) were administered to patients at a single center undergoing elective TKA before surgery, and at 6 and 12 months after surgery. Latent class growth mixture models were used to analyze the patterns of change in PROMs scores over time. Multinomial logistic regression was used to investigate the association between patient characteristics and PROMs trajectories. Results A total of 564 patients were included in the study. The analysis highlighted differential patterns of improvement after TKA. Three distinct PROMs trajectories were identified for each PROMs questionnaire, with one trajectory indicating the most favorable outcome. Female gender appears to be associated with a presentation to surgery with worse perceived quality of life and joint function than males, but also more rapid improvement after surgery. Having an ASA score greater than 3 is instead associated with a worse functional recovery after TKA. Conclusion The results suggest three main PROMs trajectories in patients undergoing elective TKA. Most patients reported improved quality of life and joint functioning at 6 months, which then stabilized. However, other subgroups showed more varied trajectories. Further research is needed to confirm these findings and to explore the potential clinical implications of these results.

Abstract Background The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up. Methods Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models. Results The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure. Conclusions Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.