Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features.

Background & Aims: The lymphatic system plays crucial roles in maintaining fluid balance and immune regulation. Studying the liver lymphatics has been considered challenging, as common lymphatic endothelial cell (LyEC) markers are expressed by other liver cells. Additionally, isolation of sufficient numbers of LyECs has been challenging because of their extremely low abundance (<0.01% of entire liver cell population) in a normal liver. Methods: Potential LyEC markers was identified using our published single-cell RNA sequencing (scRNA-seq) dataset (GSE147581) in mouse livers. Interleukin-7 (IL7) promoter-driven green fluorescent protein knock-in heterozygous mice were used for the validation of IL7 expression in LyECs in the liver, for the development of liver LyEC isolation protocol, and generating liver ischemia/reperfusion (I/R) injury. Scanning electron microscopy was used for the structural analysis of LyECs. Changes in LyEC phenotypes in livers of mice with I/R were determined by RNA-seq analysis. Results: Through scRNA-seq analysis, we have identified IL7 as an exclusive marker for liver LyECs, with no overlap with other liver cell types. Based on IL7 expression in liver LyECs, we have established an LyEC isolation method and observed distinct cell surface structures of LyECs with fenestrae and cellular pores (ranging from 100 to 400 nm in diameter). Furthermore, we identified LyEC genes that undergo alterations during I/R liver injuries. Conclusions: This study not only identified IL7 as an exclusively expressed gene in liver LyECs, but also enhanced our understanding of LyEC structures and demonstrated transcriptomic changes in injured livers. Impact and implications: Understanding the lymphatic system in the liver is challenging because of the absence of specific markers for liver LyEC. This study has identified IL7 as a reliable marker for LyECs, enabling the development of an effective method for their isolation, elucidating their unique cell surface structure, and identifying LyEC genes that undergo changes during liver damage. The development of IL7 antibodies for detecting it in human liver specimens will further advance our understanding of the liver lymphatic system in the future.

Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, non-destructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here we report a completely different mechanism by which neutrophils act non-destructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy subjects. This non-destructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.

Tracing the Impact of Domestic Storage Conditions on Antioxidant Activity and Lipid Profiles in the Edible Microalgae Chlorella vulgaris and Tetraselmis chui.

The microalgae Chlorella vulgaris and Tetraselmis chui are valued for their nutrient-rich content, including lipids and polyunsaturated fatty acids (PUFA). However, little is known about how storage and processing affect their lipid quality. This study aimed to assess the impact of domestic storage and cooking practices in dried biomass of C. vulgaris and T. chui. Four conditions were tested: control (newly opened package), light (storage at room temperature and daily light regimen for three weeks), frozen (storage in the freezer at -20 °C for three weeks), and heated (three cycles of 90 min at 100 °C). Lipid extracts were analyzed by GC-MS and LC-MS, and antioxidant activity through DPPH and ABTS radical scavenging assays. Tested storage conditions promoted a decrease in fatty acid content and in diacyl/lyso lipid species ratios of phospholipid (PC/LPC, PE/LPE) and betaine lipids (DGTS/MGTS). Lipid extracts from light treatment showed the lowest antioxidant activity in C. vulgaris (ABTS, IC40: 104.9; DPPH, IC20: 187.9 ± 15.0), while heat affected the antioxidant activity of T. chui (ABTS, IC40: 88.5 ± 2.8; DPPH, IC20 209.4 ± 10.9). These findings underscore the impact of managing storage and processing conditions to optimize the nutritional and functional benefits of C. vulgaris and T. chui in food and feed applications.

Unravelling the mechanisms of organic micropollutant removal in bio-electrochemical systems: Insights into sorption, electrochemical degradation, and biodegradation processes.

Bio-electrochemical systems (BESs) have recently been proposed as an efficient treatment technology to remove organic micropollutants from water treatment plants. In this study, we aimed to differentiate between sorption, electrochemical transport/degradation, and biodegradation. Using electro-active microorganisms and electrodes, we investigated organic micropollutant removal at environmentally relevant concentrations, clarifying the roles of sorption and electrochemical and biological degradation. The role of anodic biofilms on the removal of 10 relevant organic micropollutants was studied by performing separate sorption experiments on carbon-based electrodes (graphite felt, graphite rod, graphite granules, and granular activated carbon) and electrochemical degradation experiments at two different electrode potentials (-0.3 and 0 V). Granular activated carbon showed the highest sorption of micropollutants; applying a potential to graphite felt electrodes increased organic micropollutant removal. Removal efficiencies >80 % were obtained for all micropollutants at high anode potentials (+0.955 V), indicating that the studied compounds were more susceptible to oxidation than to reduction. All organic micropollutants showed removal when under bio-electrochemical conditions, ranging from low (e.g. metformin, 9.3 %) to exceptionally high removal efficiencies (e.g. sulfamethoxazole, 99.5 %). The lower removal observed under bio-electrochemical conditions when compared to only electrochemical conditions indicated that sorption to the electrode is key to guarantee high electrochemical degradation. The detection of transformation products of chloridazon and metformin indicated that (bio)-electrochemical degradation occurred. This study confirms that BES can treat some organic micropollutants through several mechanisms, which merits further investigation.

A dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models.

A defining feature of systemic lupus erythematosus (SLE) is loss of tolerance to self-DNA, and DNASE1L3 deficiency, the main enzyme responsible for chromatin degradation in blood, is also associated with SLE. This association includes an ultra-rare pediatric population with DNASE1L3 deficiency who develop SLE, adult patients with loss of function variants of DNASE1L3 who are at a higher risk for SLE, and patients with sporadic SLE who have neutralizing autoantibodies to DNASE1L3. To mitigate the pathogenic effects of inherited and acquired DNASE1L3 deficiencies, we engineered a long-acting enzyme biologic with dual DNASE1/DNASE1L3 activity that is resistant to DNASE1 and DNASE1L3 inhibitors. Notably, we found that the biologic prevented the development of lupus in Dnase1-/-/Dnase1L3-/- double knockout mice and rescued animals from death in pristane-induced lupus. Finally, we confirmed that the human isoform of the enzyme biologic was not recognized by autoantibodies in SLE and efficiently degrades genomic and mitochondrial cell free DNA, as well as microparticle DNA, in SLE plasma. Our findings suggest that autoimmune diseases characterized by aberrant DNA accumulation, such as SLE, can be effectively treated with a replacement DNASE tailored to bypass pathogenic mechanisms, both genetic and acquired, that restrict DNASE1L3 activity.

Co-occurrence of PRKN and SYNJ1 variants in Early-Onset Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM_004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM_003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD.

Subjective and Objective Monitoring Markers: Are They Related to Game Performance Indicators in Elite Female Volleyball Players?

PURPOSE: This cohort study aimed to investigate the relationship between subjective (wellness and internal training load [ITL]) and objective (neuromuscular fatigue) monitoring markers and performance aspects (reception quality [RQ] and attack efficiency [AE]) in professional female volleyball players. METHODS: The study was conducted over an 8-week period during the final mesocycle of the competitive phase. A total of 24 training sessions and 10 matches were included in the analysis. Subjective measures of wellness and ITL were assessed, and neuromuscular fatigue was evaluated using countermovement-jump (CMJ) height. RQ and AE were determined based on game statistics. RESULTS: The study found a positive relationship between wellness and RQ, particularly affecting outside hitters and liberos. ITL showed a positive association with AE, primarily impacting outside hitters, opposite hitters, and middle blockers. Additionally, ITL demonstrated a negative correlation with RQ, mainly affecting outside hitters and liberos. CMJ performance was associated with AE, where a decrease in CMJ height was linked to reduced AE. CONCLUSIONS: The findings highlight the importance of considering players' wellness scores in training and match strategies for different positions. Careful management of training loads, considering both physical and technical demands, is crucial for optimizing performance outcomes. Monitoring neuromuscular fatigue, as indicated by CMJ performance, is particularly relevant for outside hitters, opposite hitters, and middle blockers involved in attack actions. Coaches, trainers, and sports practitioners can use these insights to develop position-specific training protocols and implement effective strategies for maintaining or improving performance metrics under various stressors.

Guillain-Barré Syndrome After a SARS-CoV-2 Vaccine.

The worldwide mass vaccination campaign against COVID-19 has been the largest one ever undertaken. Although the short-term safety profile of the different vaccines has been well established, neuroinflammatory complications have been described, including rare cases of acute demyelinating inflammatory polyneuropathy. We report a 63-year-old man who presented to the emergency department with proximal muscle weakness and paresthesia. He had received the first dose of the AZD1222 SARS-CoV-2 vaccine (Oxford, AstraZeneca) two weeks before presentation. The diagnosis of Guillain-Barré syndrome (GBS) was confirmed by clinical features, cerebrospinal fluid analysis, and electromyography. On the second hospital day, progression to flaccid tetraplegia, cranial nerve involvement, and respiratory failure, requiring invasive mechanical ventilation, were noted, and he was admitted to the intensive care unit. Despite the prompt diagnosis and immunosuppressive treatment initiation, the patient was left with severe disability. Although the COVID-19 vaccination was generally safe and socially beneficial, individual adverse reactions, including neuroinflammatory severe complications, may occur.

Corrigendum: Assessing MR-compatibility of somatosensory stimulation devices: a systematic review on testing methodologies.

[This corrects the article DOI: 10.3389/fnins.2023.1071749.].

Study of Body Composition and Motor Skills of Futsal Athletes of Different Competitive Levels.

This study aimed to verify whether there are differences in the body composition, functionality, lower-limb power, agility, and cardiorespiratory capacity in futsal players, comparing futsal athletes by competitive level. The athletes (N = 84) were divided into three groups: group Elite (N = 29), group Sub-Elite (N = 29), and group Non-Elite (N = 26). Anthropometric variables were analyzed through a bioimpedance scale (Inbody 270), and functionality was analyzed through a functional movement screen battery. The power of the lower limbs was tested with the Abalakov jump, the agility with the zigzag agility test, and the cardiorespiratory capacity through the futsal intermittent endurance test. Anthropometric data from futsal athletes revealed a homogeneity in relation to the variables analyzed, regardless of the level of competition in which they operate. In performance variables, the power of the members and functionality was considered a discriminating factor of the level of competitiveness of the athletes, with the Elite group athletes presenting the best values. We concluded that there were no differences in relation to the body composition of the athletes. However, the athletes of higher levels, as a rule, present better performances in physiological aspects, results that can be explained by the fact that there is a better periodization in terms of training, with more intense loads and more complex competitive calendars, thus resulting in a greater specialization of these athletes.

The association between referral by specialists in oral diagnosis on survival rates of patients with oral cancer: A retrospective cohort study.

BACKGROUND: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer. METHODS: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival. RESULTS: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival. CONCLUSION: Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.

The Effectiveness of Osseodensification Drilling versus the Conventional Surgical Technique on Implant Stability: A Clinical Trial.

Background/Objective: To ensure that implants are able to support prosthetic rehabilitation, a stable and functional union between the bone and the implant surface is crucial to its stability and success. To increase bone volume and density and excel bone-implant contact, a novel drilling method, called osseodensification (OD), was performed. To assess the effectiveness of the osseodensification drilling protocol versus the conventional surgical technique on implant stability. Methods: Bone Level Tapered Straumann implants were placed side-by-side with both OD and subtractive conventional drilling (SD) in 90 patients from CESPU-Famalicão clinical unit. IT was measured using a manual torque wrench, and the Implant stability quotient (ISQ) value was registered using the Osstell® IDX. Results: According to the multifactorial ANOVA, there were statistically significant differences in the mean IT values due to the arch only (F(1.270) = 4.702, p-value = 0.031 < 0.05). Regarding the length of the implant, there were statistically significant differences in the mean IT in the OD group (p = 0.041), with significantly lower mean IT values for the Regular implants compared to the Long. With respect to the arch, the analyses of the overall ISQ values showed an upward trend in both groups in the maxilla and mandible. High levels of IT also showed high ISQ values, which represent good indicators of primary stability. Conclusions: OD does not have a negative influence on osseointegration compared to conventional subtractive osteotomy.

The Use of Solid Sodium Silicate as Activator for an Amorphous Wollastonitic Hydraulic Binder.

To ensure the acceptable mechanical strength of amorphous wollastonitic hydraulic binders (AWHs), activation with a sodium silicate solution is necessary. However, the use of this type of activator increases the final cost and the complexity of the product's overall use. In this work, we focus on enhancing the manufacturing of the alkaline activator by producing three Na2SiO3 powders using cost-effective raw materials. The procedure consisted of heating a mixture of NaOH pebbles with either sand, glass, or diatomite to a temperature of 330 °C for 2 h. After synthesis, the powders were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Diffraction (XRD) techniques. Finally, mortars made with AWHs were activated using the synthesized powders that were added either as a solid or dissolved in an aqueous solution. The compressive strength results in these mortars show that the lab-made activators are competitive with the traditional sodium silicate activators. Furthermore, the synthetized activators can be added in either solid form or pre-dissolved in a solution. This innovative approach represents a more economical, sustainable and easy-to-use approach to enhancing the competitiveness of AWHs.

Epidemiology and Burden of Ventilator-Associated Pneumonia among Adult Intensive Care Unit Patients: A Portuguese, Multicenter, Retrospective Study (eVAP-PT Study).

Ventilator-associated pneumonia (VAP) is a prevailing nosocomial infection in critically ill patients requiring invasive mechanical ventilation (iMV). The impact of VAP is profound, adversely affecting patient outcomes and placing a significant burden on healthcare resources. This study assessed for the first time the contemporary VAP epidemiology in Portugal and its burden on the healthcare system and clinical outcomes. Additionally, resource consumption (duration of iMV, intensive care unit (ICU), hospital length of stay (LOS)) and empirical antimicrobial therapy were also evaluated. This multicenter, retrospective study included patients admitted to the hospital between July 2016 and December 2017 in a participating ICU, who underwent iMV for at least 48 h. Patients with a VAP diagnosis were segregated for further analysis (n = 197). Control patients, ventilated for >48 h but without a VAP diagnosis, were also included in a 1:1 ratio. Cumulative VAP incidence was computed. All-cause mortality was assessed at 28, 90, and 365 days after ICU admission. Cumulative VAP incidence was 9.2% (95% CI 8.0-10.5). The all-cause mortality rate in VAP patients was 24.9%, 34.0%, and 40.6%, respectively, and these values were similar to those observed in patients without VAP diagnosis. Further, patients with VAP had significantly longer ICU (27.5 vs. 11.0 days, p < 0.001) and hospital LOS (61 vs. 35.9 days, p < 0.001), more time under iMV (20.7 vs. 8.0 days, p < 0.001) and were more often subjected to tracheostomy (36.5 vs. 14.2%; p < 0.001). Patients with VAP who received inappropriate empirical antimicrobials had higher 28-day mortality, 34.3% vs. 19.5% (odds ratio 2.16, 95% CI 1.10-4.23), although the same was not independently associated with 1-year all-cause mortality (p = 0.107). This study described the VAP impact and burden on the Portuguese healthcare system, with approximately 9% of patients undergoing iMV for >48 h developing VAP, leading to increased resource consumption (longer ICU and hospital LOS). An unexpectedly high incidence of inappropriate, empirical antimicrobial therapy was also noted, being positively associated with a higher mortality risk of these patients. Knowledge of the Portuguese epidemiology characterization of VAP and its multidimensional impact is essential for efficient treatment and optimized long-term health outcomes of these patients.

Atrial Fibrillation in Critically Ill Patients: Incidence and Outcomes.

BACKGROUND: Atrial fibrillation (AF), either chronic or new onset, is common in critically ill patients. Its epidemiology and relationship with clinical outcomes are poorly known. OBJECTIVE: To understand the burden of AF in patients admitted to the ICU and its impact on patients' outcomes. METHODS: This is a single-center, retrospective cohort study evaluating all patients with AF admitted to a non-cardiac intensive care unit over the course of 54 months. Clinical outcomes were evaluated in the short (hospital discharge) and long term (two-year follow-up). The hazard ratio (HR) with 95% CI was computed for the whole population as well as for propensity score-matched patients, with or without AF. RESULTS: A total of 1357 patients were screened (59.1% male), with a mean age of 75 ± 15.2 years, length of intensive care unit stay of 4.7 ± 5.1 days, and hospital mortality of 26%. A diagnosis of AF was found in 215 patients (15.8%), 142 of whom had chronic AF. The hospital all-cause mortality was similar in patients with chronic or new-onset AF (31% vs. 28.8%, p = 0.779). Patients with AF had higher in-hospital, one-year, and two-year crude mortality (30.2% vs. 22.9%, p = 0.024; 47.9% vs. 35.3%, p = 0.001; 52.6% vs. 38.4%, p < 0.001). However, after propensity score matching (N = 213), this difference was no longer significant for in-hospital mortality (OR: 1.17; 95% CI: 0.77-1.79), one-year mortality (OR: 1.38; 95% CI: 0.94-2.03), or two-year mortality (OR: 1.30; 95% CI: 0.89-1.90). CONCLUSIONS: In ICU patients, the prevalence of AF, either chronic or new-onset, was 15.8%, and these patients had higher crude mortality. However, after adjustment for age and severity on admission, no significant differences were found in the short- and long-term mortality.

Functional and structural connectivity success predictors of real-time fMRI neurofeedback targeting DLPFC: Contributions from central executive, salience, and default mode networks.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF), a training method for the self-regulation of brain activity, has shown promising results as a neurorehabilitation tool, depending on the ability of the patient to succeed in neuromodulation. This study explores connectivity-based structural and functional success predictors in an NF n-back working memory paradigm targeting the dorsolateral prefrontal cortex (DLPFC). We established as the NF success metric the linear trend on the ability to modulate the target region during NF runs and performed a linear regression model considering structural and functional connectivity (intrinsic and seed-based) metrics. We found a positive correlation between NF success and the default mode network (DMN) intrinsic functional connectivity and a negative correlation with the DLPFC-precuneus connectivity during the 2-back condition, indicating that success is associated with larger uncoupling between DMN and the executive network. Regarding structural connectivity, the salience network emerges as the main contributor to success. Both functional and structural classification models showed good performance with 77% and 86% accuracy, respectively. Dynamic switching between DMN, salience network and central executive network seems to be the key for neurofeedback success, independently indicated by functional connectivity on the localizer run and structural connectivity data.

Beyond the Jump: A Scoping Review of External Training Load Metrics in Volleyball.

CONTEXT: Volleyball is a complex sport involving multifaceted movements and high-velocity actions, leading to diverse external training loads (ETLs) that have profound implications for player performance and injury risk. OBJECTIVE: To provide a comprehensive overview of the measurement of ETL in volleyball, identify gaps in current understanding, and offer valuable insights for stakeholders in the field. DATA SOURCES: The literature search was conducted across the following electronic databases: PubMed/Medline, Scopus, Web of Science, and SPORTDiscus. STUDY SELECTION: Studies were selected based on their relevance to the measurement of ETL in volleyball. STUDY DESIGN: A scoping review methodology was chosen to map and summarize the broad body of literature related to ETL measurement in volleyball. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Data related to ETL measurements in volleyball were extracted and analyzed from the selected studies, focusing on metrics utilized, player positions examined, and technologies employed. RESULTS: A total of 18 studies related to ETL in volleyball were identified and examined for this review. Despite the importance of sagittal plane movements in volleyball, the review identified a substantial research gap regarding ETL measurements beyond this plane, as well as a lack of focus on the unique demands of different player positions like the liberos. The use of technologies such as inertial measurement units was prevalent, but more comprehensive measurement methods are needed. CONCLUSION: There is a critical need for diversified ETL metrics in volleyball, extending beyond the conventional sagittal plane measurements. The findings highlight a substantial research gap in addressing the unique demands of different player positions, notably the liberos. This study underscores the importance of incorporating multiplanar movement data, player-specific roles, and advanced measurement technologies to develop more tailored training programs and injury prevention strategies.

Neurofeedback training of executive function in autism spectrum disorder: distinct effects on brain activity levels and compensatory connectivity changes.

BACKGROUND: Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. METHODS: Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. RESULTS: The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. CONCLUSIONS: Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

A prolonged intensive care unit stay defines a worse long-term prognosis - Insights from the critically ill mortality by age (Cimba) study.

BACKGROUND: Patients with critical illness often survive the intensive care unit (ICU) at a cost of prolonged length of stay (LOS) and slow recovery. This chronic critically ill disease may lead to long-term poor outcomes, especially in older or frail patients. OBJECTIVES: The main goal of this study was to address the characteristics and outcomes of patients with prolonged ICU LOS. Mainly, short- and long-term admissions were compared to identify risk factors for persistent critical illness and to characterise the impact on ICU, hospital, and long-term mortality. METHODS: Subanalysis of a retrospective, multicentric, observational study addressing the 2-year outcome of patients admitted to Portuguese ICUs (the Cimba study). Patients were segregated according to an ICU LOS of ≥14 days. RESULTS: Data from 37 118 patients were analysed, featuring a median ICU LOS of 4 days (percentile: 25-75 2-9), and a mortality of 16.1% in the ICU, 24.0% in the hospital, and 38.7% after 2 years. A total of 5334 patients (14.4%) had an ICU LOS of ≥14 days (corresponding to 48.9% of all ICU patients/days). Patients with prolonged LOS were more often younger (52.8% vs 46.4%, were ≤65 years of age , p < 0.001), although more severe (Simplified Acute Physiology Score II: 49.1 ± 16.9 vs 41.8 ± 19.5, p < 0.001), and had higher ICU and hospital mortality (18.3% vs 15.7%, and 31.2 vs 22.8%, respectively). Prolonged ICU LOS was linked to an increased risk of dying during the 2-year follow-up (adjusted Cox proportional hazard: 1.65, p < 0.001). CONCLUSION: Prolonged LOS is associated with a long-term impact on patient prognosis. More careful planning of care should incorporate these data.