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Abstract Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.

BackgroundExtended reality (XR), encompassing technologies such as virtual reality, augmented reality, and mixed reality, has rapidly gained prominence in health care. However, existing XR research often lacks rigor, proper controls, and standardization. ObjectiveTo address this and to enhance the transparency and quality of reporting in early-phase clinical evaluations of XR applications, we present the “Reporting for the early-phase clinical evaluation of applications using extended reality” (RATE-XR) guideline. MethodsWe conducted a 2-round modified Delphi process involving experts from diverse stakeholder categories, and the RATE-XR is therefore the result of a consensus-based, multistakeholder effort. ResultsThe guideline comprises 17 XR-specific (composed of 18 subitems) and 14 generic reporting items, each with a complementary Explanation & Elaboration section. ConclusionsThe items encompass critical aspects of XR research, from clinical utility and safety to human factors and ethics. By offering a comprehensive checklist for reporting, the RATE-XR guideline facilitates robust assessment and replication of early-stage clinical XR studies. It underscores the need for transparency, patient-centeredness, and balanced evaluation of the applications of XR in health care. By providing an actionable checklist of minimal reporting items, this guideline will facilitate the responsible development and integration of XR technologies into health care and related fields.

AI holds the potential to transform healthcare, promising improvements in patient care. Yet, realizing this potential is hampered by over-reliance on limited datasets and a lack of transparency in validation processes. To overcome these obstacles, we advocate the creation of a detailed registry for AI algorithms. This registry would document the development, training, and validation of AI models, ensuring scientific integrity and transparency. Additionally, it would serve as a platform for peer review and ethical oversight. By bridging the gap between scientific validation and regulatory approval, such as by the FDA, we aim to enhance the integrity and trustworthiness of AI applications in healthcare.

Abstract Despite artificial intelligence (AI) technology progresses at unprecedented rate, our ability to translate these advancements into clinical value and adoption at the bedside remains comparatively limited. This paper reviews the current use of implementation outcomes in randomized controlled trials evaluating AI-based clinical decision support and found limited adoption. To advance trust and clinical adoption of AI, there is a need to bridge the gap between traditional quantitative metrics and implementation outcomes to better grasp the reasons behind the success or failure of AI systems and improve their translation into clinical value.

Human T-Lymphotropic Virus type-1 (HTLV-1) is a unique retrovirus associated with both leukemogenesis and a specific neuroinflammatory condition known as HTLV-1-Associated Myelopathy (HAM). Currently, most proposed HAM biomarkers require invasive CSF sampling, which is not suitable for large cohorts or repeated prospective screening. To identify non-invasive biomarkers for incident HAM in a large Brazilian cohort of PLwHTLV-1 (n=615 with 6,673 person-years of clinical follow-up), we selected all plasma samples available at the time of entry in the cohort (between 1997–2019), in which up to 43 cytokines/chemokines and immune mediators were measured. Thus, we selected 110 People Living with HTLV-1 (PLwHTLV-1), of which 68 were neurologically asymptomatic (AS) at baseline and 42 HAM patients. Nine incident HAM cases were identified among 68 AS during follow-up. Using multivariate logistic regression, we found that lower IL-10, IL-4 and female sex were independent predictors of clinical progression to definite HAM (AUROC 0.91), and outperformed previously suggested biomarkers age, sex and proviral load (AUROC 0.77). Moreover, baseline IL-10 significantly predicted proviral load dynamics at follow-up in all PLwHTLV-1. In an exploratory analysis, we identified additional plasma biomarkers which were able to discriminate iHAM from either AS (IL6Rα, IL-27) or HAM (IL-29/IFN-λ1, Osteopontin, and TNFR2). In conclusion, female sex and low anti-inflammatory IL-10 and IL-4 are independent risk factors for incident HAM in PLwHTLV-1,while proviral load is not, in agreement with IL-10 being upstream of proviral load dynamics. Additional candidate biomarkers IL-29/IL-6R/TNFR2 represent plausible therapeutic targets for future clinical trials in HAM patients.

Abstract The field of ecology has undergone a molecular revolution, with researchers increasingly relying on DNA‐based methods for organism detection. Unfortunately, these techniques often require expensive equipment, dedicated laboratory spaces and specialized training in molecular and computational techniques; limitations that may exclude field researchers, underfunded programmes and citizen scientists from contributing to cutting‐edge science. It is for these reasons that we have designed a simplified, inexpensive method for field‐based molecular organism detection—FINDeM (Field‐deployable Isothermal Nucleotide‐based Detection Method). In this approach, DNA is extracted using chemical cell lysis and a cellulose filter disc, followed by two body‐heat inducible reactions—recombinase polymerase amplification and a CRISPR‐Cas12a fluorescent reporter assay—to amplify and detect target DNA, respectively. Here, we introduce and validate FINDeM in detecting Batrachochytrium dendrobatidis, the causative agent of amphibian chytridiomycosis, and show that this approach can identify single‐digit DNA copies from epidermal swabs in under 1 h using low‐cost supplies and field‐friendly equipment. This research signifies a breakthrough in ecology, as we demonstrate a field‐deployable platform that requires only basic supplies (i.e. micropipettes, plastic consumables and a UV flashlight), inexpensive reagents (~$1.29 USD/sample) and emanated body heat for highly sensitive, DNA‐based organism detection. By presenting FINDeM in an ecological system with pressing, global biodiversity implications, we aim to not only highlight how CRISPR‐based applications promise to revolutionize organism detection but also how the continued development of such techniques will allow for additional, more diversely trained researchers to answer the most pressing questions in ecology.

Background: Quercetin (QR) is one of the major constituents of the methanolic extract of the leaves of Psidium guajava (Guava leaves). Objectives: The work’s aim is to understand the Quercetin’s mechanism in improving insulin resistance, use the homeostasis model assessment for insulin resistance (HOMA-IR) to determine the influence of quercetin on glycemic control, Look at how quercetin affects diabetes-related lipid metabolism and lipid profile measures. Analyze the impact of QR on oxidative stress in diabetic rats and contrast its antidiabetic effects whether administered as a nutrient or supplement. Materials and methods: Sixty adult male Wister rats that were matched in age and had starting body weights between 150 and 200 g were used in this study. One normoglycemic control group and 3 diabetic control groups (15 rats per group) were used. The diabetic control rats received the vehicle orally as saline daily, the normoglycemic control group received quercetin orally in a dose of 50 mg/kg per day, and the diabetic rats received quercetin orally in a dose of 100 mg/kg per day. Results: After six weeks of therapy, the rats with diabetes receiving isolated quercetin at doses of 50 and 100 mg/kg had reduced blood glucose levels, and their triglyceride, low-density lipoprotein, and total cholesterol profiles all significantly improved. Also, there was significant decrease homeostatic model assessment for insulin resistance, serum transaminases, hepatic malondialdehyde, and HMG CoA expression in liver and a substantial rise in levels of insulin, hepatic GSH, and insulin receptor substrate (IRS2) expression & Phosphoinositide 3-kinases in liver as compared to those of control group, but non- significance changes in high-density lipoprotein, AKT expression in liver were observed. Conclusions: Quercetin could be considered as a potential hypoglycmeic medication with possible mechanisms controlling the hyperglycemic state and cholesterol, triglycerides and LDL levels.

Background: During the development of human T-cell lymphotropic virus (HTLV-1)-associated myelopathy (HAM), the inflammatory phenomenon is very prominent and is a major factor in the outcome of the disease. The use of corticosteroids can modify their natural history, and in this study, we evaluated the effectiveness of using daily low-dose prednisone. Methods: This was a cross-sectional study using data collected by physicians monitoring patients with HAM at the Institute of Infectious Diseases “Emilio Ribas”, the main referral center for patients with infectious diseases in São Paulo, Brazil. The objective was to determine if daily low-dose oral prednisone would be able to stabilize the progression of HAM. The outcome measure was a change in the Osame Motor Disability Score (OMDS). Results: Fifty-four patients used treatment with oral prednisone, 5 milligrams daily. Nine cases were excluded from the study because they did not have at least two rating scales within a minimum interval of one year, and six were excluded for being co-infected with HIV and/or HCV. Thirty-nine patients met this criterion and were included for analysis. The majority were women (71.8%), the mean age was 56.51 years old (SD ± 9.74), and the median time of use of prednisone was 16 months. Thirty-two patients (82.05%) maintained the same OMDS, 5/39 (12.82%) had clinical worsening, and 2/39 (5.13%) improved. Conclusions: There was a trend toward clinical stability with the use of oral corticosteroids. However, randomized controlled trials are necessary to evaluate the use in clinical practices in all stages of HAM.

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurological and clinical manifestations that do not meet diagnostic criteria for HAM. These conditions may later progress to HAM or constitute an intermediate clinical form: intermediate syndrome (IS), a mid-point between asymptomatic HTLV-1 carriers and those with full myelopathy. Thus, we determined the incidence of HAM cases in the HTLV-1-asymptomatic and IS patients, and the clinical/laboratory associated markers. A total of 204 HTLV-1-positive patients were included in this study, divided into two groups: Group 1, including 145 asymptomatic HTLV-1 subjects (ASY), and Group 2, including 59 patients with inflammatory clinical symptoms in more than three systems and a high proviral load (PVL). During a 60-month follow-up time, with the age ranging from 47 to 79 years, ten patients of the fifty-nine initially diagnosed as IS developed HAM (iHAM), and two patients of the initial 145 ASY developed HAM directly. Women were more prevalent in all groups. For the iHAM patients, the age ranged from 20 to 72 years, with a mean of 53 (±15 SD). Older age was associated with the development of HAM, higher PVL and IS; however, there was no any specific symptom or clinical sign, that was associated with risk for iHAM. In conclusion, IS cases could be an early phase of development of HAM. These findings show the presence of higher incidence probabilities in our cohort than previously reported.

Abstract The Gulf of California is known for its high productivity, diversity, and unique oceanography. Based on old and recent contributions, we estimate a richness of 160 copepod species in this province. This work seeks to identify latitudinal and seasonal patterns of the copepod composition, abundance, and diversity in the Gulf of California during 1985. Differences between four zones of the gulf (NGC, CGC, SGC, EGC) and between the cold and warm seasons were hypothesized, based on taxonomic and ecological data. Samples were collected during the CORTES cruises (1985), which also measured salinity, temperature, and dissolved oxygen at each station. We analyzed the latitudinal and seasonal variation of the copepod community with multivariate analyses (NMDS-PCA) and correlated these with the environmental data (CCA). Seventy-nine copepod species were identified, averaging 265,649 and 98,885 ind/10 m3 in the cold and warm seasons, respectively. Only 53 of these occurred in both seasons, indicating seasonal change in species composition. Composition and diversity varied latitudinally in the cold season (P < 0.05 in all comparisons but CGC vs. SGC), but not in the warm season (except NGC vs. the rest of the gulf). There was seasonal change in the composition and the abundance (P < 0.005 cold vs. warm season). Richness and diversity were negatively correlated with salinity (decreasing from the north of the gulf); the abundance and composition were mainly affected by the shift in temperature. These patterns also match the phytoplankton abundance and size structure in the gulf, probably the main factors affecting copepod distribution.

Land use and land cover (LULC) mapping initiatives are essential to support decision making related to the implementation of different policies. There is a need for timely and accurate LULC maps. However, building them is challenging. LULC changes affect natural areas and local biodiversity. When they cause landscape fragmentation, the mapping and monitoring of changes are affected. Due to this situation, improving the efforts for LULC mapping and monitoring in fragmented biomes and ecosystems is crucial, and the adequate separability of classes is a key factor in this process. We believe that combining multidimensional Earth observation (EO) data cubes and spectral vegetation indices (VIs) derived from the red edge, near-infrared, and shortwave infrared bands provided by the Sentinel-2/MultiSpectral Instrument (S2/MSI) mission reduces uncertainties in area estimation, leading toward more automated mappings. Here, we present a low-cost semi-automated classification scheme created to identify croplands, pasturelands, natural grasslands, and shrublands from EO data cubes and the Surface Reflectance to Vegetation Indexes (sr2vgi) tool to automate spectral index calculation, with both produced in the scope of the Brazil Data Cube (BDC) project. We used this combination of data and tools to improve LULC mapping in the Brazilian Cerrado biome during the 2018–2019 crop season. The overall accuracy (OA) of our results is 88%, indicating the potential of the proposed approach to provide timely and accurate LULC mapping from the detection of different vegetation patterns in time series.

Arterial dysfunction is major risk factor for cardiovascular complications, and arterial stiffness is an independent risk factor in end-stage renal disease patients. As the distance from the heart increases, arterial stiffness (pulse wave velocity) becomes progressively more marked. This generates a centrifugal stiffness gradient, which leads to partial, continuous local wave reflections, which in turn attenuate the transmission of pulsatile pressure into the microcirculation, thus limiting the potentially deleterious outcomes both upstream (on the heart: left-ventricular hypertrophy and coronary perfusion) and downstream (on the renal and cerebral microcirculation: reduced glomerular filtration and impaired cognitive functions). The impact of arterial aging is greater on the aorta and central capacitive arteries, and it is characterized by a loss or reversal of the physiological stiffness gradient between central and peripheral arteries. Recently, however, in contrast to observations on the aorta, several studies have shown less pronounced, absent, or even negative associations between muscular peripheral arteries and age–stiffness relationships, which may be associated with a decrease in or reversal of the stiffness gradient. These findings point to a potential benefit of assessing the muscular peripheral arteries to predict the risk of cardiovascular disease and suggest that reversal of the stiffness gradient may be an independent risk factor for all-cause mortality.

Abstract Background HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. Patients and methods We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. Results We found that systemic IL-6 was positively correlated with both age (r = 0.50, p

Games practiced by Erotes and children are known mainly by a series of small paintings in the Casa dei Cervi of Herculanum. These scenes allow the reconstruction of the gestures, material, and the number of players involved in these games, thus completing the information taken from literary sources, often lacunary. Among the many painted games, the ephedrismos is particularly well represented in other domestic contexts in Pompeii, such as the Casa dei Vettii, the Casa dei Pittori al lavoro and the Casa del Bracciale d’oro. This paper shows the reception of this Greek game “par excellence” in pictorial art as well as in ludic Roman practices.

Abstract Background Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. Methods We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 ‘wave’ in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. Results We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80–0.84]) compared to the National early warning score (0.72 [0.69–0.74]) and the Modified early warning score (0.67 [0.65–0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [− 0.09 to 0.14], slope = 0.79 [0.73–0.86]). Conclusions This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed.

Grégory Ben-Sadoun,1,2 Emeline Michel,3,4 Cédric Annweiler,1,5– 7 Guillaume Sacco3,5,8 1Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital of Angers, Angers, France; 2Normandie Université, UNICAEN, INSERM, COMETE, CYCERON, CHU Caen, Caen, 14000, France; 3Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, Clinique Gériatrique du Cerveau et du Mouvement, Nice, France; 4Université Côte d’Azur, LAMHESS, Nice, France; 5Laboratoire de Psychologie des Pays de la Loire, Univ Angers, Université de Nantes, EA 4638 LPPL, SFR CONFLUENCES, Angers, F-49000, France; 6School of Medicine, Health Faculty, University of Angers, Angers, France; 7Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada; 8Université Côte d’Azur, CoBTek, Nice, FranceCorrespondence: Grégory Ben-SadounDepartment of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital of Angers, Angers, FranceEmail bensadoun.gregory@hotmail.fr; gregory.bensadoun@chu-angers.fr; gregory.ben-sadoun@unicaen.frAbstract: Systems using passive infrared sensors with a low resolution were recently proposed to answer the dilemma effectiveness–ethical considerations for human fall detection by Information and Communication Technologies (ICTs) in older adults. How effective is this type of system? We performed a systematic review to identify studies that investigated the metrological qualities of passive infrared sensors with a maximum resolution of 16× 16 pixels to identify falls. The search was conducted on PubMed, ScienceDirect, SpringerLink, IEEE Xplore Digital Library, and MDPI until November 26– 28, 2020. We focused on studies testing only these types of sensor. Thirteen articles were “conference papers”, five were “original articles” and one was a found in arXiv.org (an open access repository of scientific research). Since four authors “duplicated” their study in two different journals, our review finally analyzed 15 studies. The studies were very heterogeneous with regard to experimental procedures and detection methods, which made it difficult to draw formal conclusions. All studies tested their systems in controlled conditions, mostly in empty rooms. Except for two studies, the overall performance reported for the detection of falls exceeded 85– 90% of accuracy, precision, sensitivity or specificity. Systems using two or more sensors and particular detection methods (eg, 3D CNN, CNN with 10-fold cross-validation, LSTM with CNN, LSTM and Voting algorithms) seemed to give the highest levels of performance (> 90%). Future studies should test more this type of system in real-life conditions.Keywords: fall detection, older adults, passive infrared sensor, thermal sensor, thermopile

Abstract Sustainable urban systems (SUS) science is a new science integrating work across established and emerging disciplines, using diverse methods, and addressing issues at local, regional, national, and global scales. Advancing SUS requires the next generation of scholars and practitioners to excel at synthesis across disciplines and possess the skills to innovate in the realms of research, policy, and stakeholder engagement. We outline key tenets of graduate education in SUS, informed by historical and global perspectives. The sketch is an invitation to discuss how graduates in SUS should be trained to engage with the challenges and opportunities presented by continuing urbanization.

Abstract While Brazil publicly committed to reduce deforestation in Amazonia at the 26th Conference of the Parties (COP26), the Brazilian parliament is moving toward weakening environmental laws. Deforestation rates continue ascending, reaching in 2021 the highest value since 2006 (13,235 km2). To overcome this paradox, strategies to curb deforestation are mandatory. The current strategy, “Plano Amazônia 21/22,” prioritizes law enforcement actions to curb illegal deforestation in only 11 Amazonian municipalities. Here, we show that this prioritization is likely to be insufficient since these municipalities account for just 37% of the current deforestation rate. This strategy may also be undermined by the leakage of deforestation actions to unmonitored municipalities. Using a set of spatially explicit datasets integrated into a deforestation‐prediction modeling approach, we propose a science‐based alternative method for ranking deforestation hotspots to be prioritized by law enforcement actions. Our prioritization method accounts for more than 60% of the deforestation, detecting larger deforested areas in both private and public lands, while covering 27% less territory than “Plano Amazônia 21/22.” Optimizing the detection of priority areas for curbing deforestation, as proposed here, is the first step to reducing deforestation rates and comply with the Brazilian legal commitment of 3925 km2 year−1.

Introduction A large proportion of patients experience a wide range of sequelae after acute COVID-19, especially after severe illness. The long-term health sequelae need to be assessed. Our objective was to longitudinally assess persistence of symptoms and clusters of symptoms up to 12 months after hospitalisation for COVID-19 and to assess determinants of the main persistent symptoms. Methods In this multicenter prospective cohort study patients with COVID-19 are followed up for 2 years with measurements at 3, 6, 12 and 24 months after hospital discharge. Here, we present interim results regarding persistent symptoms up to 12 months. Results We included 492 patients; mean±sd age was 60.2±10.7 years, 335 (68.1%) were males, median length of hospital stay was 11 (6.0–27.0) days. At 3 months after discharge 97.0% of the patients had at least one persisting symptom, this declined to 95.5% and 92.0% at 6 and 12 months, respectively (p=0.010). Muscle weakness, exertional dyspnoea, fatigue, and memory and concentration problems were the most prevalent symptoms with rates over 50% during follow-up. Over time, muscle weakness, hair loss and exertional dyspnoea decreased significantly (p

Increasing yield resiliency under water deficits remains a high priority for crop improvement. In considering the yield benefit of a plant trait modification, two facts are often overlooked: (1) the total amount of water available to a crop through a growing season ultimately constrains growth and yield cannot exceed what is possible with the limited amount of available water, and (2) soil water content always changes over time, so plant response needs to be considered within a temporally dynamic context of day-to-day variation in soil water status. Many previous evaluations of drought traits have implicitly considered water deficit from a “static” perspective, but while the static approach of stable water deficit treatments is experimentally congruous, the results are not realistic representations of real-world drought conditions, where soil water levels are always changing. No trait always results in a positive response under all drought scenarios. In this paper, we suggest two key traits for improving grain legume yield under water deficit conditions: (1) partial stomata closure at elevated atmospheric vapor pressure deficit that results in soil water conservation, and (2) lessening of the high sensitivity of nitrogen fixation activity to soil drying.

Abstract Background First studies indicate that up to 6 months after hospital discharge, coronavirus disease 2019 (COVID-19) causes severe physical, cognitive, and psychological impairments, which may affect participation and health-related quality of life (HRQoL). After hospitalization for COVID-19, a number of patients are referred to medical rehabilitation centers or skilled nursing facilities for further treatment, while others go home with or without aftercare. The aftercare paths include 1] community-based rehabilitation; 2] in- and outpatient medical rehabilitation; 3] inpatient rehabilitation in skilled nursing facilities; and 4] sheltered care (inpatient). These aftercare paths and the trajectories of recovery after COVID-19 urgently need long-term in-depth evaluation to optimize and personalize treatment. CO-FLOW aims, by following the outcomes and aftercare paths of all COVID-19 patients after hospital discharge, to systematically study over a 2-year period: 1] trajectories of physical, cognitive, and psychological recovery; 2] patient flows, healthcare utilization, patient satisfaction with aftercare, and barriers/facilitators regarding aftercare as experienced by healthcare professionals; 3] effects of physical, cognitive, and psychological outcomes on participation and HRQoL; and 4] predictors for long-term recovery, health care utilization, and patient satisfaction with aftercare. Methods CO-FLOW is a multicenter prospective cohort study in the mid-west of the Netherlands with a 2-year follow-up period. Measurements comprise non-invasive clinical tests and patient reported outcome measures from a combined rehabilitation, pulmonary, and intensive care perspective. Measurements are performed at 3, 6, 12, and 24 months after hospital discharge and, if applicable, at rehabilitation discharge. CO-FLOW aims to include at least 500 patients who survived hospitalization for COVID-19, aged ≥18 years. Discussion CO-FLOW will provide in-depth knowledge on the long-term sequelae of COVID-19 and the quality of current aftercare paths for patients who survived hospitalization. This knowledge is a prerequisite to facilitate the right care in the right place for COVID-19 and comparable future infectious diseases. Trial registration The Netherlands Trial Register (NTR), https://www.trialregister.nl . Registered: 12-06-2020, CO-FLOW trialregister no. NL8710.

Abstract Climate change is increasing variability in precipitation patterns in many parts of the globe. Unpredictable changes in water availability can be particularly challenging for organisms that rely on precipitation‐fed water sources for completing their life cycle, such as many amphibian species. Although developmental plasticity can mitigate the impacts of changing environments for some species, this strategy can come at a cost to other fitness‐linked traits, such as immune function. We investigated localized variation in the capacity to respond to pond drying and evaluated whether developmental responses induced carry‐over effects in disease susceptibility in three leopard frog species (Rana [Lithobates] pipiens and Rana sphenocephala; two populations each, and one population of Rana chiricahuensis). Using mesocosms located near the site of collection (

Introduction A substantial proportion of intensive care unit (ICU) survivors develop psychological impairments after ICU treatment, part of the postintensive care syndrome, resulting in a decreased quality of life. Recent data suggest that an ICU-specific virtual reality intervention (ICU-VR) for post-ICU patients is feasible and safe, improves satisfaction with ICU aftercare, and might improve psychological sequelae. In the present trial, we firstly aim to determine whether ICU-VR is effective in mitigating post-traumatic stress disorder (PTSD)-related symptoms and secondly to determine the optimal timing for initiation with ICU-VR.Methods and analysis This international, multicentre, randomised controlled trial will be conducted in 10 hospitals. Between December 2021 and April 2023, we aim to include 300 patients who have been admitted to the ICU ≥72 hours and were mechanically ventilated ≥24 hours. Patients will be followed for 12 consecutive months. Patients will be randomised in a 1:1:1 ratio to the early ICU-VR group, the late ICU-VR group, or the usual care group. All patients will receive usual care, including a mandatory ICU follow-up clinic visit 3 months after ICU discharge. Patients in the early ICU-VR group will receive ICU-VR within 2 weeks after ICU discharge. Patients in the late VR group will receive ICU-VR during the post-ICU follow-up visit. The primary objective is to assess the effect of ICU-VR on PTSD-related symptoms. Secondary objectives are to determine optimal timing for ICU-VR, to assess the effects on anxiety-related and depression-related symptoms and health-related quality of life, and to assess patient satisfaction with ICU aftercare and perspectives on ICU-VR.Ethics and dissemination The Medical Ethics Committee United, Nieuwegein, the Netherlands, approved this study and local approval was obtained from each participating centre (NL78555.100.21). Our findings will be disseminated by presentation of the results at (inter)national conferences and publication in scientific, peer-reviewed journals.Trial registration number NL9812.

Abstract Background The SARS-CoV-2 outbreak has resulted in a tremendous increase in hospital and intensive care unit (ICU) admissions all over the world. Patients with severe coronavirus disease 2019 (COVID-19) warranting ICU treatment usually have prolonged mechanical ventilation and are expected to be prone to develop psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety and depression, which negatively impact quality of life. To date, no effective treatment strategy is available. In the current trial, we aim to assess the effect of an ICU-specific virtual reality (ICU-VR) intervention on psychological well-being and quality of life after COVID-19 ICU treatment. Methods In this multicentre, randomized controlled trial, we aim to examine whether COVID-19-specific ICU-VR, offered 3 months after hospital discharge, improves psychological well-being and quality of life. Secondary objectives are, firstly, to examine the intra-group changes in psychological well-being and quality of life and the inter-group differences in psychological well-being and quality of life during follow-up, up to 12 months after hospital discharge, and secondly, to examine patients’ satisfaction with and rating of ICU care and aftercare and patients’ perspectives on ICU-VR. Eighty adult patients treated for COVID-19 in the mixed-surgical ICUs of four hospitals in Rotterdam, the Netherlands, will be included and randomized (1:1) to either early or late ICU-VR between June 29 and December 31, 2020. Patients randomized to early ICU-VR will receive the ICU-VR intervention during an outpatient clinic visit 3 months after hospital discharge, whereas patients randomized to late ICU-VR will receive ICU-VR 6 months after hospital discharge. Primary outcomes of this study are psychological well-being, assessed using the Impact of Event Scale–Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), and quality of life, assessed using the European Quality of Life 5 Dimensions (EQ-5D) and RAND-36 questionnaires, up to 6 months after hospital discharge. Discussion Currently, an effective treatment for psychological sequelae after ICU treatment for specific illnesses is unavailable. Results from this study will provide insight whether virtual reality is a modality that can be used in ICU aftercare to improve psychological well-being and quality of life, or satisfaction, after ICU treatment for specific illnesses such as COVID-19. Trial registration This trial has been retrospectively registered on the Netherlands Trial Register on August 14, 2020 ( NL8835 ).

Abstract Background Diabetic macular edema (DME) is a major cause of visual impairment and its treatment is a public health challenge. Even though anti-angiogenic drugs are the gold-standard treatment, they are not ideal and subthreshold laser (SL) remains a viable and promising therapy in selected cases. The aim of this study was to evaluate its efficacy in a real-life setting. Methods Retrospective case series of 56 eyes of 36 patients with center-involving DME treated with SL monotherapy. Treatment was performed in a single session with the EasyRet® photocoagulator with the following parameters: 5% duty cycle, 200-ms pulse duration, 160-µm spot size and 50% power of the barely visible threshold. A high-density pattern was then applied to the whole edematous area, using multispot mode. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were obtained at baseline and around 3 months after treatment. Results Fifty-six eyes of 36 patients were included (39% women, mean age 64.8 years old); mean time between treatment day and follow-up visit was 14 ± 6 weeks. BCVA (Snellen converted to logMAR) was 0.59 ± 0.32 and 0.43 ± 0.25 at baseline and follow-up, respectively (p = 0.002). Thirty-two percent had prior panretinal photocoagulation (p = 0.011). Mean laser power was 555 ± 150 mW and number of spots was 1,109 ± 580. Intraretinal and subretinal fluid (SRF) was seen in 96 and 41% of eyes at baseline and improved in 35 and 74% of those after treatment, respectively. Quantitative analysis of central macular thickness (CMT) change was performed in a subset of 23 eyes, 43% of which exhibited > 10% CMT reduction post-treatment. Conclusions Subthreshold laser therapy is known to have RPE function as its main target, modulating the activation of heat-shock proteins and normalizing cytokine expression. In the present study, the DME cases associated with SRF had the best anatomical response, while intraretinal edema responded poorly to laser monotherapy. BCVA and macular thickness exhibited a mild response, suggesting the need for combined treatment in most patients. Given the effect on SRF reabsorption, subthreshold laser therapy could be a viable treatment option in selected cases.

Abstract Background Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient’s post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. Methods In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. Results A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). Conclusions In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention.

Objective Although the role of artificial intelligence (AI) in medicine is increasingly studied, most patients do not benefit because the majority of AI models remain in the testing and prototyping environment. The development and implementation trajectory of clinical AI models are complex and a structured overview is missing. We therefore propose a step-by-step overview to enhance clinicians’ understanding and to promote quality of medical AI research.Methods We summarised key elements (such as current guidelines, challenges, regulatory documents and good practices) that are needed to develop and safely implement AI in medicine.Conclusion This overview complements other frameworks in a way that it is accessible to stakeholders without prior AI knowledge and as such provides a step-by-step approach incorporating all the key elements and current guidelines that are essential for implementation, and can thereby help to move AI from bytes to bedside.

BackgroundAlthough psychological sequelae after intensive care unit (ICU) treatment are considered quite intrusive, robustly effective interventions to treat or prevent these long-term sequelae are lacking. Recently, it was demonstrated that ICU-specific virtual reality (ICU-VR) is a feasible and acceptable intervention with potential mental health benefits. However, its effect on mental health and ICU aftercare in COVID-19 ICU survivors is unknown. ObjectiveThis study aimed to explore the effects of ICU-VR on mental health and on patients’ perceived quality of, satisfaction with, and rating of ICU aftercare among COVID-19 ICU survivors. MethodsThis was a multicenter randomized controlled trial. Patients were randomized to either the ICU-VR (intervention) or the control group. All patients were invited to an COVID-19 post-ICU follow-up clinic 3 months after hospital discharge, during which patients in the intervention group received ICU-VR. One month and 3 months later (4 and 6 months after hospital discharge), mental health, quality of life, perceived quality, satisfaction with, and rating of ICU aftercare were scored using questionnaires. ResultsEighty-nine patients (median age 58 years; 63 males, 70%) were included. The prevalence and severity of psychological distress were limited throughout follow-up, and no differences in psychological distress or quality of life were observed between the groups. ICU-VR improved satisfaction with (mean score 8.7, SD 1.6 vs 7.6, SD 1.6 [ICU-VR vs control]; t64=–2.82, P=.006) and overall rating of ICU aftercare (mean overall rating of aftercare 8.9, SD 0.9 vs 7.8, SD 1.7 [ICU-VR vs control]; t64=–3.25; P=.002) compared to controls. ICU-VR added to the quality of ICU aftercare according to 81% of the patients, and all patients would recommend ICU-VR to other ICU survivors. ConclusionsICU-VR is a feasible and acceptable innovative method to improve satisfaction with and rating of ICU aftercare and adds to its perceived quality. We observed a low prevalence of psychological distress after ICU treatment for COVID-19, and ICU-VR did not improve psychological recovery or quality of life. Future research is needed to confirm our results in other critical illness survivors to potentially facilitate ICU-VR’s widespread availability and application during follow-up. Trial RegistrationNetherlands Trial Register NL8835; https://www.trialregister.nl/trial/8835 International Registered Report Identifier (IRRID)RR2-10.1186/s13063-021-05271-z

Trichoderma is recognized as a prolific producer of nonribosomal peptides (NRPs) known as peptaibols, which have remarkable biological properties, such as antimicrobial and anticancer activities, as well as the ability to promote systemic resistance in plants against pathogens. In this study, the sequencing of 11-, 14- and 15-res peptaibols produced by a marine strain of Trichoderma isolated from the ascidian Botrylloides giganteus was performed via liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Identification, based on multilocus phylogeny, revealed that our isolate belongs to the species T. endophyticum, which has never been reported in marine environments. Through genome sequencing and genome mining, 53 biosynthetic gene clusters (BGCs) were identified as being related to bioactive natural products, including two NRP-synthetases: one responsible for the biosynthesis of 11- and 14-res peptaibols, and another for the biosynthesis of 15-res. Substrate prediction, based on phylogeny of the adenylation domains in combination with molecular networking, permitted extensive annotation of the mass spectra related to two new series of 15-res peptaibols, which are referred to herein as “endophytins”. The analyses of synteny revealed that the origin of the 15-module peptaibol synthetase is related to 18, 19 and 20-module peptaibol synthetases, and suggests that the loss of modules may be a mechanism used by Trichoderma species for peptaibol diversification. This study demonstrates the importance of combining genome mining techniques, mass spectrometry analysis and molecular networks for the discovery of new natural products.

Over the last 15 years, urine treatment technologies have developed from lab studies of a few pioneers to an interesting innovation, attracting attention from a growing number of process engineers. In this broad review, we present literature from more than a decade on biological, physical-chemical and electrochemical urine treatment processes. Like in the first review on urine treatment from 2006, we categorize the technologies according to the following objectives: stabilization, volume reduction, targeted N-recovery, targeted P-recovery, nutrient removal, sanitization, and handling of organic micropollutants. We add energy recovery as a new objective, because extensive work has been done on electrochemical energy harvesting, especially with bio-electrochemical systems. Our review reveals that biological processes are a good choice for urine stabilization. They have the advantage of little demand for chemicals and energy. Due to instabilities, however, they are not suited for bathroom applications and they cannot provide the desired volume reduction on their own. A number of physical-chemical treatment technologies are applicable at bathroom scale and can provide the necessary volume reduction, but only with a steady supply of chemicals and often with high demand for energy and maintenance. Electrochemical processes is a recent, but rapidly growing field, which could give rise to exciting technologies at bathroom scale, although energy production might only be interesting for niche applications. The review includes a qualitative assessment of all unit processes. A quantitative comparison of treatment performance was not the goal of the study and could anyway only be done for complete treatment trains. An important next step in urine technology research and development will be the combination of unit processes to set up and test robust treatment trains. We hope that the present review will help guide these efforts to accelerate the development towards a mature technology with pilot scale and eventually full-scale implementations.

We present the results of three field tests and three laboratory tests of a new physical-chemical urine treatment system, which can recover all nutrients, while pathogens are inactivated. The system consists of two steps. In the first reactor, biological processes including urea hydrolysis are prevented by mixing fresh urine with calcium hydroxide (Ca(OH)2). Due to the high pH value and the high availability of calcium, phosphate can be recovered by precipitation. The high pH value also fosters the inactivation of microorganisms, including pathogens. In the second reactor, water is evaporated at low energy consumption by blowing unheated ambient air over the stabilized urine. Stabilization in the first reactor was successful in all field and laboratory tests. The pH value remained between 12 and 13, except for short dips due to shortages of Ca(OH)2. Nearly all phosphorus (92-96%) precipitated and could be recovered as calcium phosphate in the first reactor, while nitrogen and potassium overflowed with the urine into the evaporation reactor. The efficiency of the second treatment step was very different for field and laboratory experiments and depended on the duration of the experiment. During a four-day laboratory test, nitrogen recovery was 98%. In contrast, nitrogen recovery was only around 20% in the long-term field experiments. The high nitrogen losses occurred, because biological urea hydrolysis was not inhibited anymore, when the pH value in the second reactor decreased due to the dissolution of high amounts of carbon dioxide from the ambient air. Potassium was not subject to any significant loss, and the measured recovery in the solid evaporation product was 98%. Evaporation rates ranged between 50 g m−2 h−1 (RH = 82±13%, T = 12±6°C) and 130 g m−2 h−1 (RH = 60±19%, T = 24±5°C) in the three field tests. Apart from some disturbances due to low supply of Ca(OH)2, the urine module functioned without any substantial failures and was simple to maintain. The minimum consumption of Ca(OH)2 at full capacity was 6 g·L−1 urine and the electricity demand was 150 Wh kg−1 water evaporated from urine, resulting in operational costs of 0.05 EUR pers−1 d−1.

OBJECTIVES:. Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU–related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients’ self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health. DESIGN:. A multicenter, randomized controlled feasibility study. SETTING:. ICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands. PATIENTS:. Consecutive mechanically ventilated patients with sepsis or septic shock. INTERVENTIONS:. Patients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group). MEASUREMENT AND MAIN RESULTS:. Explorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5–21 d) after ICU discharge, and one session (median, 95% range, 1–6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36–67] vs control virtual reality, 47 [26–63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life. CONCLUSIONS:. ICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.

OBJECTIVES:. To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors. DESIGN:. A prospective, observational cohort study. SETTING:. Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands. PATIENTS:. Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic. MEASURES AND MAIN RESULTS:. The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36–77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0–17] vs 5 [0–16]; estimated mean difference 2.3 [95% CI, 0.0–4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0–15] vs 5 [0–16]; estimated mean difference 2.4 [95% CI, 0.1–2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population. CONCLUSIONS:. Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.

Grégory Ben-Sadoun,1,2 Emeline Michel,3,4 Cédric Annweiler,1,5–7 Guillaume Sacco3,5,8 1Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital of Angers, Angers, France; 2Normandie Université, UNICAEN, INSERM, COMETE, CYCERON, CHU Caen, Caen, 14000, France; 3Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, Clinique Gériatrique du Cerveau et du Mouvement, Nice, France; 4Université Côte d’Azur, LAMHESS, Nice, France; 5LPPL, Laboratoire de Psychologie des Pays de la Loire, Univ Angers, Université de Nantes, EA 4638 LPPL, SFR CONFLUENCES, Angers, F-49000, France; 6School of Medicine, Health Faculty, University of Angers, Angers, France; 7Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada; 8Université Côte d’Azur, CoBTek, Nice, FranceCorrespondence: Grégory Ben-Sadoun, Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital of Angers, Angers, France, Email gregory.ben-sadoun@unicaen.fr View the original paper by Dr Ben-Sadoun and colleagues This is in response to the Letter to the Editor

Background: Non-invasive tests leading to elective coronary angiography (CAG) have low diagnostic yield for obstructive coronary heart disease (CHD). Aortic stiffness, an independent predictor of CHD events can be easily measured by pulse wave velocity (PWV). We aimed at retrospectively evaluating the diagnostic accuracy PWV index to detect CHD in consecutive patients with suspected CHD that underwent CAG. Method: In population of 86 healthy patients with available PWV data, a theoretical PWV was derived. In different population of 62 individuals who underwent CAG for suspected CHD, PWV index was calculated as index [(measured PWV – theoretical PWV)/theoretical PWV]. Logistic regression and comparisons between ROC curves were used to add value of CAG indication performance of PWV index. Results: Out of 62, seventeen patients presented obstructive CHD and 22 patients had non-obstructive CHD. PWV index and severity of CHD were positively correlated (p

Abstract A paracentesis prior to an intravitreal injection is a very safe procedure and can prevent IOP-spikes after injections. As these spikes pose the risk of inducing glaucomatous changes particularly in patients with frequent injections and/or with a risk profile, a regular paracentesis prior to an injection may be considered and discussed with the patient.

Decapods are one of the most diverse crustacean orders, with around 17,500 extant species [...]

Objectives:. ICU treatments frequently result in long-term psychologic impairments, negatively affecting quality of life. An effective treatment strategy is still lacking. The aim of this study was to describe and evaluate the safety and immersiveness of a newly designed ICU-specific virtual reality module. Design:. A randomized controlled healthy volunteer trial. Setting:. ICU of the Franciscus Gasthuis & Vlietland Hospital (Rotterdam, the Netherlands), a large teaching hospital. Participants:. Forty-five virtual reality–naive healthy volunteers. Interventions:. Volunteers were randomized to three arms: the head-mounted display virtual reality group (n = 15), the 2D group (n = 15), and the crossover group (n = 15). Safety was assessed by changes in vital signs and the occurrence of simulator sickness (Simulator Sickness Questionnaire). Immersiveness was assessed using the Igroup Presence Questionnaire. Measurements and Main Results:. Volunteers in the head-mounted display virtual reality group experienced more mild symptoms of simulator sickness, expressed as symptoms of dizziness (p = 0.04) and stomach awareness (p = 0.04), than the 2D group. Nevertheless, none of the individual Simulator Sickness Questionnaire items were scored as being severe, no changes in vital signs were observed, and no sessions were prematurely stopped. Volunteers in the crossover group experienced a higher total presence (p < 0.001) when using head-mounted display virtual reality, expressed as a higher sense of presence (p < 0.001), more involvement (p < 0.01), and more experienced realism (p < 0.001). Conclusions:. ICU-specific virtual reality appears safe and more immersive than 2D, implicating that ICU-specific virtual reality is feasible for clinical use. One should however be aware of simulator sickness-related symptoms. Future research is needed to confirm these findings in survivors of critical illness.

ABSTRACT The human T cell lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered. Since then, it has spread worldwide and is mainly associated with adult T cell leukemia/lymphoma (ATLL) and HTLV1-associated myelopathy (HAM). Its relationship, however, with other types of cancer is controversial. We describe the case of a patient presenting with small cells lung epidermoid carcinoma who had recently developed HAM, and a review of the literature related to these conditions. This is the first case of this type of lung cancer, the same of the first description in the literature, associated with HAM outside Japan.

Introduction In the current situation, clinical patient data are often siloed in multiple hospital information systems. Especially in the intensive care unit (ICU), large volumes of clinical data are routinely collected through continuous patient monitoring. Although these data often contain useful information for clinical decision making, they are not frequently used to improve quality of care. During, but also after, pressing times, data-driven methods can be used to mine treatment patterns from clinical data to determine the best treatment options from a hospitals own clinical data.Methods In this implementer report, we describe how we implemented a data infrastructure that enabled us to learn in real time from consecutive COVID-19 ICU admissions. In addition, we explain our step-by-step multidisciplinary approach to establish such a data infrastructure.Conclusion By sharing our steps and approach, we aim to inspire others, in and outside ICU walls, to make more efficient use of data at hand, now and in the future.

A substantial number of ICU survivors are expected due to the SARS-CoV-2 outbreak, who are at risk for psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety, and depression. We designed a COVID-19 intensive care unit-specific virtual reality (ICU-VR) intervention and tested it on one of our COVID-19 patients. The impact of event scale-revised and the hospital anxiety and depression scale showed that this patient suffered from PTSD, anxiety, and depression on the day of the intervention. One week after receiving ICU-VR, levels of PTSD, anxiety and depression had normalized, and stayed normalized until 6 months after discharge. In conclusion, innovative technologies, such as VR, have the potential to improve psychological rehabilitation, and should therefore be considered by clinicians for the treatment of ICU-related psychological sequelae after COVID-19.