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The goal of this study was to explore the development and implementation of a protocol for real-time fMRI neurofeedback (rtfMRI-nf) and to assess the potential for enhancing the selective brain activation using stimuli from Virtual Reality (VR). In this study we focused on two specific brain regions, supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). Publications by other study groups have suggested impaired function in these specific brain regions in patients with the diagnoses Attention Deficit Hyperactivity Disorder (ADHD) and Tourette’s Syndrome (TS). This study explored the development of a protocol to investigate if attention and contextual memory may be used to systematically strengthen the procedure of rtfMRI-nf.

Abstract A popular and widely suggested measure for assessing unilateral hand motor skills in stroke patients is the box and block test (BBT). Our study aimed to create an augmented reality enhanced version of the BBT (AR-BBT) and evaluate its correlation to the original BBT for stroke patients. Following G-power analysis, clinical examination, and inclusion–exclusion criteria, 31 stroke patients were included in this study. AR-BBT was developed using the Open Source Computer Vision Library (OpenCV). The MediaPipe's hand tracking library uses a palm and a hand landmark machine learning model to detect and track hands. A computer and a depth camera were employed in the clinical evaluation of AR-BBT following the principles of traditional BBT. A strong correlation was achieved between the number of blocks moved in the BBT and the AR-BBT on the hemiplegic side (Pearson correlation = 0.918) and a positive statistically significant correlation (p = 0.000008). The conventional BBT is currently the preferred assessment method. However, our approach offers an advantage, as it suggests that an AR-BBT solution could remotely monitor the assessment of a home-based rehabilitation program and provide additional hand kinematic information for hand dexterities in AR environment conditions. Furthermore, it employs minimal hardware equipment.

Abstract Background/Aims Older age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults. Methods Seventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65–85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups. Results The users performed, on average, 39.8 sessions (range 1–100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants’ sex, age, and years of education. The differences in CNS Vital Signs’ global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant. Conclusions VR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size. Trial registration Clinicaltrials.gov ID NCT05369897.

BackgroundVirtual reality (VR) has emerged as a promising technology for enhancing the health care of older individuals, particularly in the domains of cognition, physical activity, and social engagement. However, existing VR products and services have limited availability and affordability; hence, there is a need for a scientifically validated and personalized VR service to be used by older adults in their homes, which can improve their overall physical, cognitive, and social well-being. ObjectiveThe main purpose of the CoSoPhy FX (Cognitive, Social, and Physical Effects) study was to analyze the effects of a VR-based digital therapeutics app on the cognitive, social, and physical performance abilities of healthy (high-functioning) older adults. This paper presents the study protocol and the results from the recruitment phase. MethodsA group of 188 healthy older adults aged 65-85 years, recruited at the Medical University of Lodz, Poland, were randomly allocated to the experimental group (VR dual-task training program) or to the control group (using a VR headset app showing nature videos). A total of 3 cognitive exercises were performed in various 360° nature environments delivered via a VR head-mounted display; the participants listened to their preferred music genre. Each patient received 3 sessions of 12 minutes per week for 12 weeks, totaling a minimum of 36 sessions per participant. Attention and working memory (Central Nervous System Vital Signs computerized cognitive battery) were used as primary outcomes, while other cognitive domains in the Central Nervous System Vital Signs battery, quality of life (World Health Organization–5 Well-Being Index), health-related quality of life (EQ-5D-5L), and anxiety (General Anxiety Disorder 7-item questionnaire) were the secondary outcomes. The group-by-time interaction was determined using linear mixed models with participants’ individual slopes. ResultsIn total, 122 (39%) of the initial 310 participants failed to meet the inclusion criteria, resulting in a recruitment rate of 61% (188/310). Among the participants, 68 successfully completed the intervention and 62 completed the control treatment. The data are currently being analyzed, and we plan to publish the results by the end of September 2024. ConclusionsVR interventions have significant potential among healthy older individuals. VR can address various aspects of well-being by stimulating cognitive functions, promoting physical activity, and facilitating social interaction. However, challenges such as physical discomfort, technology acceptance, safety concerns, and cost must be considered when implementing them for older adults. Further research is needed to determine the long-term effects of VR-based interventions, optimal intervention designs, and the specific populations that would benefit most. Trial RegistrationClinicalTrials.gov NCT05369897; https://clinicaltrials.gov/study/NCT05369897 International Registered Report Identifier (IRRID)DERR1-10.2196/53261

Alzheimer’s disease, the most common neurodegenerative disease, affects more than 60 million people worldwide, a number that is estimated to double by 2050. Alzheimer’s disease is characterized by progressive memory loss, the impairment of behavior, and mood changes, as well as the disturbed daily routine of the patient. Although there are some active molecules that can be beneficial by halting the progression of the disease, the blood–brain barrier and other physiological barriers hinder their delivery and, consequently, the appropriate management of the disease. Therefore, drug delivery systems that effectively target and overcome the blood–brain barrier to reach the targeted brain area would improve treatment effectiveness. Liposomes are lipophilic carriers that consist of a phospholipid bilayer structure, simulating the physiological lipidic layer of the blood–brain barrier and enabling better delivery of the drug to the brain. Given that pure liposomes may have less targeting affinity than functionalized liposomes, modification with groups such as lactoferrin, poly(ethylene glycol), and transferrin may improve specificity. In this mini-review, we summarize the literature on the use of liposomes for the treatment of Alzheimer’s disease, focusing on the functionalization moieties of liposomes. In addition, challenges in brain delivery are also discussed.

Training load monitoring is a common practice in sports medicine for supporting athletes’ health and performance. Despite progress in exercise oncology research for breast cancer patients, training load monitoring is underutilized. This study retrospectively investigated the relationship between maintained training load within a defined range and physical and health outcomes of ten breast cancer patients during active anticancer treatment who underwent a 12-week exercise program. Intervention consisted of endurance and resistance training, three times a week, with each session lasting 30–45 min. Assessments were conducted at baseline, 6 and 12 weeks after enrollment, evaluating physical function (6-min walk test–6MWT, and sit-to-stand), muscle strength, body composition, sleep quality (Pittsburgh Sleep Quality Index–Pittsburgh Sleep Quality Index), quality of life (EORTC-QLQ-C30), heart rate variability and physical activity levels (International Physical Activity Questionnaire–International Physical Activity Questionnaire). The Physiological Cost Index/Energy Expenditure Index (PCI/EEI) was estimated using the 6MWT and Heart rate. Training load monitoring was performed by session rating of perceived exertion (sRPE, relative intensity multiplying with session duration). Acute-to-Chronic Workload Ratio (ACWR) (7:28, rolling average) was calculated accordingly. Analyses were performed within-subjects across time points and between-subjects, comparing those who maintained from weeks 6–12 an ACWR of 0.8–1.3 with those who did not. Adherence rates were similar between groups. Physical function improved in the total sample with large effect sizes (Δ6MWT = 56.5 m [95%CI: 6–100 m], effect size [w] = 0.52, p = 0.006; ΔSit-to-Stand = 1.5 [95%CI: 1–5], effect size [w] = 0.681, p < 0.001), demonstrating greater changes in patients with higher ACWR. Sleep quality improvements were higher in the appropriate ACWR group (p = 0.016). A positive correlation was demonstrated between global health status and 6MWT change from baseline to 12 weeks (ρ = 0.689, p = 0.04). Despite a small sample size, patients maintaining sufficient relative training load presented greater physical fitness and sleep quality improvements. Thus, training load monitoring may enhance exercise program benefits in breast cancer patients under active treatment.

Abstract Background The Alzheimer’s and Music Therapy (ALMUTH) study is the first randomised controlled trial (RCT) design with 12 months of active non-pharmacological therapy (NPT) implementing music therapy (MT) and physical activity (PA) for participants with Alzheimer’s disease (AD). The aim of the present article is to retrospectively examine the inclusion of mild-to-moderate Alzheimer’s Disease patients into the main ALMUTH study protocol and to determine if continued inclusion of AD patients is warranted. Methods The randomised pilot trial was conducted as a parallel three-arm RCT, reflecting the experimental design of the ALMUTH study. The trial was conducted in Bergen, Norway, and randomisation (1:1:1) was performed by an external researcher. The study was open label and the experimental design features two active NPTs: MT and PA, and a passive control (no intervention, CON) in Norwegian speaking patients with AD who still live at home and could provide informed consent. Sessions were offered once per week (up to 90 min) up to 40 sessions over 12 months. Baseline and follow-up tests included a full neuropsychological test battery and three magnetic resonance imaging (MRI) measurements (structural, functional, and diffusion weighted imaging). Feasibility outcomes were assessed and were determined as feasible if they met the target criteria. Results Eighteen participants with a diagnosis of mild-to-moderate AD were screened, randomised, and tested once at baseline and once after 12-months. Participants were divided into three groups: MT (n = 6), PA (n = 6), and CON (n = 6). Results of the study revealed that the ALMUTH protocol in patients with AD was not feasible. The adherence to the study protocol was poor (50% attended sessions), with attrition and retention rates at 50%. The recruitment was costly and there were difficulties acquiring participants who met the inclusion criteria. Issues with study fidelity and problems raised by staff were taken into consideration for the updated study protocol. No adverse events were reported by the patients or their caregivers. Conclusions The pilot trial was not deemed feasible in patients with mild-to-moderate AD. To mitigate this, the ALMUTH study has expanded the recruitment criteria to include participants with milder forms of memory impairment (pre-AD) in addition to expanding the neuropsychological test battery. The ALMUTH study is currently ongoing through 2023. Trial registration Norsk Forskningsråd (NFR) funded. Regional Committees for Medical and Health Research Ethics (REC-WEST: reference number 2018/206). ClinicalTrials.gov: NCT03444181 (registered retrospectively 23 February 2018, https://clinicaltrials.gov/ct2/show/NCT03444181 ).

The data about the optimal duration of antibiotics and the usefulness of corticosteroids in the management of parapneumonic effusion and pleural infection are scarce. Two randomised controlled trials evaluating short antibiotic courses (ODAPE and SLIM) and another trial assessing the benefit from corticosteroid use (STOPPE) in this setting were recently published. The aim of this journal club is to present these trials and discuss their significance and limitations. ODAPE compared the efficacy and safety of a short (2 weeks) versus an extended (3 weeks) course of amoxicillin–clavulanate in community-acquired complicated parapneumonic effusions, while SLIM compared the efficacy and safety of short (14–21 days) versus longer (28–42 days) antibiotic courses in patients with community- or hospital-acquired pleural infection. STOPPE assessed the benefit from dexamethasone use in patients with community-acquired pneumonia and concomitant pleural effusion. Both ODAPE and SLIM found that shorter antibiotic courses produce less adverse events while being equally efficacious to the longer courses in a subgroup of patients, such as those with pleural infection that is stabilised with only medical treatment and does not require surgery. In contrast, STOPPE found no benefit from the use of dexamethasone in unselected patients with pneumonia and pleural effusion. Due to the significant limitations of these trials, further studies are required to confirm these findings. Commentary on: Hassan M, et al. The Short versus Long Antibiotic Course for Pleural Infection Management (SLIM) randomised controlled open-label trial. ERJ Open Res 2023; 9: 00635-2022. Porcel JM, et al. Two vs. three weeks of treatment with amoxicillin–clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial. Pleura Peritoneum 2020; 5: 20190027. Fitzgerald DB, et al. Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): a pilot randomized clinical trial. Am J Respir Crit Care Med 2022; 205: 1093–1101.

Summary: Kynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. Here, we show that the KMO product 3-hydroxykynurenine primes innate immune signaling to exacerbate systemic inflammation during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma 3-hydroxykynurenine levels that prime inflammatory gene transcription. 3-Hydroxykynurenine synergizes with interleukin-1β to cause cellular apoptosis. Critically, mice with elevated 3-hydroxykynurenine succumb fatally earlier and more readily to experimental AP. Therapeutically, blockade with the highly selective KMO inhibitor GSK898 rescues the phenotype, reducing 3-hydroxykynurenine and protecting against critical illness and death. Together, our findings establish KMO and 3-hydroxykynurenine as regulators of inflammation and the innate immune response to sterile inflammation. During critical illness, excess morbidity and death from multiple organ failure can be rescued by systemic KMO blockade.

Classical ballet dancers are exposed daily to physically demanding movements. Among these, the Grand Plié stands out for its biomechanical complexity, particularly the stress applied to the knee joint. This study investigates the knee kinematics of healthy professional classical ballet dancers performing the Grand Plié. Twenty dancers were evaluated with a motion analysis system using a marker-based protocol. Before measurements, the self-reported Global Knee Functional Assessment Scale was delivered for the knees’ functional ability, and the passive range of knee motion was also assessed. The average score on the Global Knee Functional Assessment Scale was 94.65 ± 5.92. During a complete circle of the Grand Plié movement, executed from the upright position, the average maximum internal rotation of the knee joint was 30.28° ± 6.16°, with a simultaneous knee flexion of 134.98° ± 4.62°. This internal rotation observed during knee flexion exceeds the typical range of motion for the joint, suggesting a potential risk for knee injuries, such as meniscal tears. The findings provide an opportunity for future kinematic analysis research, focusing on the movement of the Grand Plié and other common ballet maneuvers. These data have the potential to yield valuable information about the knee kinematics concerning meniscus damage.

Hybrid nanofluids contain more than one type of nanoparticle and have shown improved thermofluidic properties compared to more conventional ones that contain a single nanocomponent. Such hybrid systems have been introduced to improve further the thermal and mass transport properties of nanoparticulate systems that affect a multitude of applications. The impact of a second particle type on the effective thermal conductivity of nanofluids is investigated here using the reconstruction of particle configurations and prediction of thermal efficiency with meshless methods, placing emphasis on the role of particle aggregation. An algorithm to obtain particle clusters of the core–shell type is presented as an alternative to random mixing. The method offers rapid, controlled reconstruction of clustered systems with tailored properties, such as the fractal dimension, the average number of particles per aggregate, and the distribution of distinct particle types within the aggregates. The nanoparticle dispersion conditions are found to have a major impact on the thermal properties of hybrid nanofluids. Specifically, the spatial distribution of the two particle types within the aggregates and the shape of the aggregates, as described by their fractal dimension, are shown to affect strongly the conductivity of the nanofluid even at low volume fractions. Cluster configurations made up of a high-conducting core and a low-conducting shell were found to be advantageous for conduction. Low fractal dimension aggregates favored the creation of long continuous pathways across the nanofluid and increased conductivity.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Abstract Statistical learning refers to the implicit mechanism of extracting regularities in our environment. Numerous studies have investigated the neural basis of statistical learning. However, how the brain responds to violations of auditory regularities based on prior (implicit) learning requires further investigation. Here, we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of processing events that are irregular based on learned local dependencies. A stream of consecutive sound triplets was presented. Unbeknown to the subjects, triplets were either (a) standard, namely triplets ending with a high probability sound or, (b) statistical deviants, namely triplets ending with a low probability sound. Participants (n = 33) underwent a learning phase outside the scanner followed by an fMRI session. Processing of statistical deviants activated a set of regions encompassing the superior temporal gyrus bilaterally, the right deep frontal operculum including lateral orbitofrontal cortex, and the right premotor cortex. Our results demonstrate that the violation of local dependencies within a statistical learning paradigm does not only engage sensory processes, but is instead reminiscent of the activation pattern during the processing of local syntactic structures in music and language, reflecting the online adaptations required for predictive coding in the context of statistical learning.