Experimental Validation of an Upper Limb Benchmarking Framework in Healthy and Post-Stroke Individuals: A Pilot Study.

In the context of neurorehabilitation, there have been rapid and continuous improvements in sensors-based clinical tools to quantify limb performance. As a result of the increasing integration of technologies in the assessment procedure, the need to integrate evidence-based medicine with benchmarking has emerged in the scientific community. In this work, we present the experimental validation of our previously proposed benchmarking scheme for upper limb capabilities in terms of repeatability, reproducibility, and clinical meaningfulness. We performed a prospective multicenter study on neurologically intact young and elderly subjects and post-stroke patients while recording kinematics and electromyography. 60 subjects (30 young healthy, 15 elderly healthy, and 15 post-stroke) completed the benchmarking protocol. The framework was repeatable among different assessors and instrumentation. Age did not significantly impact the performance indicators of the scheme for healthy subjects. In post-stroke subjects, the movements presented decreased smoothness and speed, the movement amplitude was reduced, and the muscular activation showed lower power and lower intra-limb coordination. We revised the original framework reducing it to three motor skills, and we extracted 14 significant performance indicators with a good correlation with the ARAT clinical scale. The applicability of the scheme is wide, and it may be considered a valuable tool for upper limb functional evaluation in the clinical routine.

Detection of inflammasome activation in liver tissue during the donation process as potential biomarker for liver transplantation.

Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains the main source of donated organs, exploration of donation after circulatory death (DCD) addresses donor scarcity but introduces challenges due to warm ischemia. While technical advances have improved outcomes, challenges persist, with a 13% mortality rate within the first year. Delving into liver transplantation complexities reveals the profound impact of molecular signaling on organ fate. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation play a pivotal role, influencing inflammatory responses. The NLRP3 inflammasome, found in hepatocytes, contributes to inflammation, fibrosis, and liver cell death. This study explores these dynamics, shedding light on potential biomarkers and therapeutic targets. Samples from 36 liver transplant patients were analyzed for ASC specks detection and inflammasome-related gene expression. Liver biopsies, obtained before and after cold ischemia storage, were processed for immunofluorescence, qRT-PCR, and Western blot. One year post-LT clinical follow-up included diagnostic procedures for complications, and global survival was assessed. Immunofluorescence detected activated inflammasome complexes in fixed liver tissues. ASC specks were identified in hepatocytes, showing a trend toward more specks in DCD livers. Likewise, inflammasome-related gene expression analysis indicated higher expression in DCD livers, decreasing after cold ischemia. Similar results were found at protein level. Patients with increased ASC specks staining exhibited lower overall survival rates, correlating with IL1B expression after cold ischemia. Although preliminary, these findings offer novel insights into utilizing direct detection of inflammasome activation in liver tissue as a biomarker. They suggest its potential impact on post-transplant outcomes, potentially paving the way for improved diagnostic approaches and personalized treatment strategies in LT.

Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.

BACKGROUND: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. METHODS: EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. RESULTS: Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. CONCLUSIONS: These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.

Operational tolerance research in liver transplantation: a bibliometric analysis using a new web resource.

Background: Operational tolerance in liver transplantation (OT-LT), defined as the graft survival with normal function in absence of immunosuppression, has been a field of intense research since the 1980s. Thereafter, tens of clinical trials and hundreds of articles have been published, making it challenging for researchers to assimilate all the information, more so outside of their disciplines. The aim of the present study was to analyze the research in OT-LT through a new web tool (https://tolerance.imib.es). Methods: We have developed a web resource that allowed the identification of the present trends and potential research avenues in OL-LT, an overview biomedical terms that were most often cited, including which journals published the most articles, and an advanced search engine that exploited all the information in these publications. Results: A total of 734 studies were analyzed until November 2023, with a mean of 15 articles published per year, a total sum of 3,751 impact factor points and a total of 26,542 citations. The analysis of citations allowed us to establish a ranking of the most prolific countries, authors, journals and institutions, in addition to the most influential publications in OT-LT. Likewise, keyword and co-occurrence analyses answered which themes involving OT-LT are the most popular, whereas cooperation analysis showed that principal authors in OT-LT form a network, although the lack of international cooperation, especially with regard to clinical trials, appears to be one of the main challenges. Conclusion: Despite its limitations, our web tool will allow both OT-LT expert and novel researchers to be able to draw a comprehensive picture of the past, present and future of OT-LT research.

Osteoporosis in psoriatic arthritis: Risk factors, insufficiency fractures and its association with the disease activity / Osteoporosis en la artritis psoriásica: factores de riesgo, fracturas por insuficiencia y su asociación con la actividad de la enfermedad

Objective: The prevalence of osteoporosis (OP) and insufficiency fractures in psoriatic arthritis (PsA) remains controversial. The aim of this study was to describe the prevalence of OP and insufficiency fractures in a representative cohort of patients with PsA, and to analyse its association with general risk factors and characteristics of the psoriatic disease in our geographical area. Methods: Multi-centric, descriptive study of patients with PsA. We recorded clinical characteristics, as well as protective and risk factors for OP and insufficiency fractures. Hip and lumbar densitometry and lateral X-ray of the spine were evaluated. Descriptive statistics for OP and risk factors were calculated. The patients with OP were compared to those without by univariate analyses, and results were adjusted by age and sex. The association of OP and fractures with clinical characteristics was analysed by logistic regression. Results: 166 patients (50 men; 116 women) were included. OP was present in 26.5%, and it was more frequent in women and patients above 50 years old. Insufficiency fractures occurred in 5.4% of the total sample. In the logistic regression, OP was associated with age over 50 [OR 3.7; 95% CI (1.2–11.6); p=.02]. No association with clinical parameters was found. The most frequent risk factors among patients with OP were vitamin D insufficiency, sedentary behaviour, low calcium intake, and active smoking. In the logistic regression, OP was associated with early menopause [OR 11.7; 95% CI (1.29–106.0); p=.029] and sedentary behaviour [OR 2.3; 95% CI (1.0–5.2); p=.049]. Conclusions: In patients with PsA, OP is more frequent in women and patients over 50 years old. A sedentary lifestyle and early menopause may add extra risk for OP. Type, duration disease, and treatments are not associated with OP or insufficiency fractures.(AU)

Objetivo: El objetivo de este estudio fue describir la prevalencia de osteoporosis (OP) y fracturas por insuficiencia en una cohorte representativa de pacientes con artritis psoriásica (APs) y analizar su asociación con factores de riesgo generales y características de la enfermedad psoriásica en nuestra área geográfica. Métodos: Estudio multicéntrico y descriptivo de pacientes con APs. Se registraron las características clínicas, así como los factores protectores y de riesgo de OP y fracturas por insuficiencia. Se evaluó la densitometría de cadera y lumbar y la radiografía lateral de columna. Se calcularon las estadísticas descriptivas de la OP y los factores de riesgo. Los pacientes con OP se compararon con los que no la tenían mediante análisis univariantes, y los resultados se ajustaron por edad y sexo. La asociación de la OP y las fracturas con las características clínicas se analizó mediante regresión logística. Resultados: Se incluyeron 166 pacientes (50 hombres; 116 mujeres). La OP estaba presente en el 26,5% y era más frecuente en mujeres y pacientes mayores de 50 años. Se produjeron fracturas por insuficiencia en el 5,4% de la muestra total. En la regresión logística la OP se asoció con la edad superior a 50 años (OR: 3,7; IC 95%: 1,2-11,6; p=0,02), con la menopausia precoz (OR: 11,7; IC 95%: 1,29-106,0; p=0,029) y el comportamiento sedentario (OR: 2,3; IC 95%: 1,0-5,2; p=0,049). Conclusiones: En pacientes con APs la OP es más frecuente en mujeres y en aquellos mayores de 50 años. Un estilo de vida sedentario y una menopausia precoz pueden añadir un riesgo adicional de OP. El tipo, la duración de la enfermedad y los tratamientos no se asocian a las fracturas OP ni a las fracturas por insuficiencia.(AU)

Osteoporosis in psoriatic arthritis: Risk factors, insufficiency fractures and its association with the disease activity.

OBJECTIVE: The prevalence of osteoporosis (OP) and insufficiency fractures in psoriatic arthritis (PsA) remains controversial. The aim of this study was to describe the prevalence of OP and insufficiency fractures in a representative cohort of patients with PsA, and to analyse its association with general risk factors and characteristics of the psoriatic disease in our geographical area. METHODS: Multi-centric, descriptive study of patients with PsA. We recorded clinical characteristics, as well as protective and risk factors for OP and insufficiency fractures. Hip and lumbar densitometry and lateral X-ray of the spine were evaluated. Descriptive statistics for OP and risk factors were calculated. The patients with OP were compared to those without by univariate analyses, and results were adjusted by age and sex. The association of OP and fractures with clinical characteristics was analysed by logistic regression. RESULTS: 166 patients (50 men; 116 women) were included. OP was present in 26.5%, and it was more frequent in women and patients above 50 years old. Insufficiency fractures occurred in 5.4% of the total sample. In the logistic regression, OP was associated with age over 50 [OR 3.7; 95% CI (1.2-11.6); p=.02]. No association with clinical parameters was found. The most frequent risk factors among patients with OP were vitamin D insufficiency, sedentary behaviour, low calcium intake, and active smoking. In the logistic regression, OP was associated with early menopause [OR 11.7; 95% CI (1.29-106.0); p=.029] and sedentary behaviour [OR 2.3; 95% CI (1.0-5.2); p=.049]. CONCLUSIONS: In patients with PsA, OP is more frequent in women and patients over 50 years old. A sedentary lifestyle and early menopause may add extra risk for OP. Type, duration disease, and treatments are not associated with OP or insufficiency fractures.

Time since liver transplant and immunosuppression withdrawal outcomes: Systematic review and individual patient data meta-analysis.

BACKGROUND & AIMS: Successful immunosuppression withdrawal (ISW) is possible for a subfraction of liver transplant (LT) recipients but the factors that define the risk of ISW failure are largely unknown. One candidate prognostic factor for ISW success or operational tolerance (OT) is longer time between LT and ISW which we term "pre-withdrawal time". To clarify the impact of pre-withdrawal time span on subsequent ISW success or failure, we conducted a systematic review with meta-analysis. METHODS: We systematically interrogated the literature for LT recipient ISW studies reporting pre-withdrawal time. Eligible articles from Embase, Medline, and the Cochrane Central Register of Controlled Trials were used for backward and forward citation searching. Pre-withdrawal time individual patient data (IPD) was requested from authors. Pooled mean differences and time-response curves were calculated using random-effects meta-analyses. RESULTS: We included 17 studies with 691 patients, 15 of which (620 patients) with IPD. Study-level risk of bias was heterogeneous. Mean pre-withdrawal time was greater by 427 days [95% confidence interval (CI) 67-788] in OT compared to non-OT patients. This increase was potentiated to 799 days (95% CI 369-1229) or 1074 days (95% CI 685-1463) when restricting analysis to adult or European study participants. In time-response meta-analysis for adult or European ISW candidates, likelihood of OT increased by 7% (95% CI 4-10%) per year after LT (GRADE low- and moderate-certainty of evidence, respectively). CONCLUSIONS: Our data support the impact of pre-withdrawal time in ISW decision-making for adult and European LT recipients. PROSPERO REGISTRATION: CRD42021272995.

Transcranial magnetic stimulation combined with endogenous human hippocampal and motor cortical activity enhances memory.

The hippocampus is a fundamental cortical structure in the memory process of encoding, retaining, and recalling information. Transcranial Magnetic Stimulation (TMS) following a Paired Associative Stimulation (PAS) enhances nervous system excitability and promotes cortical plasticity mechanisms by synchronizing two stimuli in the same neural pathway. However, PAS has not been shown to improve memorization capacity yet. Here, we present an innovative protocol stemming from the PAS paradigm, which combines single-pulse TMS to the hippocampus with endogenous hippocampal activity during a working memory (WM) task. 96 volunteers were randomized across one experimental group and three parallel groups (motor cortex stimulation, sham stimulation, and no stimulation) in a single session. This combined-stimuli configuration resulted in an increased memorization capacity in the WM task, which was dependent on the stimulated brain location and subjects' basal memory performance. These results are potentially significant for clinical research on memory dysfunction and its related neurological disorders. Future research on paired associative or combined stimulation is required to unveil stimulation-derived neural mechanisms that enhance the ability to memorize.

Automatic Detection of Magnetic Disturbances in Magnetic Inertial Measurement Unit Sensors Based on Recurrent Neural Networks.

This paper proposes a new methodology for the automatic detection of magnetic disturbances from magnetic inertial measurement unit (MIMU) sensors based on deep learning. The proposed approach considers magnetometer data as input to a long short-term memory (LSTM) neural network and obtains a labeled time series output with the posterior probabilities of magnetic disturbance. We trained our algorithm on a data set that reproduces a wide range of magnetic perturbations and MIMU motions in a repeatable and reproducible way. The model was trained and tested using 15 folds, which considered independence in sensor, disturbance direction, and signal type. On average, the network can adequately detect the disturbances in 98% of the cases, which represents a significant improvement over current threshold-based detection algorithms.

Virtual Physical Coupling of Two Lower-Limb Exoskeletons.

Physical interaction between individuals plays an important role in human motor learning and performance during shared tasks. Using robotic devices, researchers have studied the effects of dyadic haptic interaction mostly focusing on the upper-limb. Developing infrastructure that enables physical interactions between multiple individuals' lower limbs can extend the previous work and facilitate investigation of new dyadic lower-limb rehabilitation schemes. We designed a system to render haptic interactions between two users while they walk in multi-joint lower-limb exoskeletons. Specifically, we developed an infrastructure where desired interaction torques are commanded to the individual lower-limb exoskeletons based on the users' kinematics and the properties of the virtual coupling. In this pilot study, we demonstrated the capacity of the platform to render different haptic properties (e.g., soft and hard), different haptic connection types (e.g., bidirectional and unidirectional), and connections expressed in joint space and in task space. With haptic connection, dyads generated synchronized movement, and the difference between joint angles decreased as the virtual stiffness increased. This is the first study where multi-joint dyadic haptic interactions are created between lower-limb exoskeletons. This platform will be used to investigate effects of haptic interaction on motor learning and task performance during walking, a complex and meaningful task for gait rehabilitation.

Components of hostility and discrimination in cardiology.

The Gender-Diverse (TGD) population in Mexico faces significant health challenges, such as limited access to healthcare and a prevalence of adverse conditions. Cardiology is crucial for this population due to a high prevalence of risk factors and cardiovascular diseases. Despite a lack of precise data, it is estimated that 0.5-1.5% of the population identifies as TGD. They encounter sociocultural challenges, including discrimination and stigma, contributing to health issues and a lack of treatment access. Cardiovascular risk factors, hormone self-administration, and barriers to healthcare access are prominent concerns. Opportunities for improvement involve strengthening medical education, implementing inclusive policies, and promoting research and data collection. The development of specific clinical guidelines and inclusive health programs is suggested. The theory of minority stress emphasizes addressing chronic psychosocial stressors and recognizing the influence of stress factors on health. Integrating healthcare services for all populations in cardiology and fostering resilience are key strategies. In summary, a comprehensive approach is needed to reduce disparities in cardiac care and enhance the health of all populations in Mexico.

La población de diferentes géneros en México se enfrenta a desafíos significativos en salud, cómo el acceso limitado a la atención médica y la prevalencia de malas condiciones. La cardiología es crucial para esta población debido a la alta prevalencia de factores de riesgo y enfermedades cardiovasculares. A pesar de la falta de datos precisos, se estima que el 0.5-1.5% de la población se identifica como transgénero. Enfrentan desafíos socioculturales, como discriminación y estigmatización que contribuyen a problemas de salud y falta de acceso a tratamientos. Los factores de riesgo cardiovascular, la autoadministración de hormonas, y las barreras en el acceso a la atención médica son preocupaciones destacadas. Las oportunidades para mejorar incluyen fortalecer la educación médica, implementar políticas inclusivas, y promover la investigación y recopilación de datos. Se sugiere el desarrollo de guías clínicas específicas y programas de salud inclusivos. La teoría de la minorización destaca la importancia de abordar tensiones psicosociales crónicas y reconocer la influencia de factores estresantes en la salud. Integrar servicios de salud para todas las poblaciones en cardiología y fomentar la resiliencia son estrategias clave. En resumen, se necesita un enfoque integral para reducir las disparidades en la atención cardíaca y mejorar la salud de todas las poblaciones en México.

The complex landscape of TMS devices: A brief overview.

The increasing application of TMS in research and therapy has spawned an ever-growing number of commercial and non-commercial TMS devices and technology development. New CE-marked devices appear at a rate of approximately one every two years, with new FDA-approved application of TMS occurring at a similar rate. With the resulting complex landscape of TMS devices and their application, accessible information about the technological characteristics of the TMS devices, such as the type of their circuitry, their pulse characteristics, or permitted protocols would be beneficial. We here present an overview and open access database summarizing key features and applications of available commercial and non-commercial TMS devices (http://www.tmsbase.info). This may guide comparison and decision making about the use of these devices. A bibliometric analysis was performed by identifying commercial and non-commercial TMS devices from which a comprehensive database was created summarizing their publicly available characteristics, both from a technical and clinical point of view. In this document, we introduce both the commercial devices and prototypes found in the literature. The technical specifications that unify these devices are briefly analysed in two separate tables: power electronics, waveform, protocols, and coil types. In the prototype TMS systems, the proposed innovations are focused on improving the treatment regarding the patient: noise cancellation, controllable parameters, and multiple stimulation. This analysis shows that the landscape of TMS is becoming increasingly fragmented, with new devices appearing ever more frequently. The review provided here can support development of benchmarking frameworks and comparison between TMS systems, inform the choice of TMS platforms for specific research and therapeutic applications, and guide future technology development for neuromodulation devices. This standardisation strategy will allow a better end-user choice, with an impact on the TMS manufacturing industry and a homogenisation of patient samples in multi-centre clinical studies. As an open access repository, we envisage the database to grow along with the dynamic development of TMS devices and applications through community-lead curation.

Muscle synergies analysis shows altered neural strategies in women with patellofemoral pain during walking.

Several studies suggest that the central nervous system coordinates muscle activation by modulating neural commands directed to groups of muscles combined to form muscle synergies. Individuals with patellofemoral pain (PFP) move differently from asymptomatic individuals. Understanding the neural strategies involved in the execution of tasks such as walking can help comprehend how the movement is planned and better understand this clinical condition. The objective of this study was to compare muscle synergies between women with and without PFP during walking. Eleven women with PFP and thirteen asymptomatic women were assessed using three-dimensional kinematics and electromyography (EMG) while walking at self-selected speed. Kinematics of the trunk, pelvis and lower limbs were analyzed through the Movement Deviation Profile. Muscle synergies were extracted from the EMG signals of eight lower limb muscles collected throughout the whole gait cycle. Kinematic differences between the two groups (p<0.001, z-score = 3.06) were more evident during loading response, terminal stance, and pre-swing. PFP group presented a lower number of muscle synergies (p = 0.037), and greater variability accounted for (VAFtotal) when using 3 (p = 0.017), 4 (p = 0.004), and 5 (p = 0.012) synergies to reconstruct all EMG signals. The PFP group also presented higher VAFmuscle for rectus femoris (p = 0.048) and gastrocnemius medialis (p = 0.019) when considering 4 synergies. Our results suggest that women with PFP show lower motor complexity and deficit in muscle coordination to execute gait, indicating that gait in PFP is the result of different neural commands compared to asymptomatic women.

Endothelial cell activation mediated by cold ischemia-released mitochondria is partially inhibited by defibrotide and impacts on early allograft function following liver transplantation.

DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect. The activation of cultured human umbilical vein endothelial cells (HUVECs) was analyzed after challenging with end-ischemic OPS (eiOPS) obtained after CIS. Additionally, transwell assays were performed to study the ability of eiOPS to attract lymphocytes across the endothelium. The study revealed that eiOPS upregulated the expression of MCP-1 and IL-6 in HUVECs. Moreover, eiOPS increased the membrane expression of ICAM-1and HLA-DR, which facilitated leukocyte migration toward a chemokine gradient. Furthermore, eiOPS demonstrated its chemoattractant ability. This activation was mediated by free mitochondria. Defibrotide was found to partially inhibit the eiOPS-mediated activation. Moreover, the eiOPS-mediated activation of endothelial cells (ECs) correlated with early allograft dysfunction in liver transplant patients. Our finding provide support for the hypothesis that mitochondria released during cold ischemia could trigger EC activation, leading to complications in graft outcomes. Therefore, the analysis and quantification of free mitochondria in the eiOPS samples obtained after CIS could provide a predictive value for monitoring the progression of transplantation. Moreover, defibrotide emerges as a promising therapeutic agent to mitigate the damage induced by ischemia in donated organs.

Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?

Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients.

Haptic Human-Human Interaction During an Ankle Tracking Task: Effects of Virtual Connection Stiffness.

While treating sensorimotor impairments, a therapist may provide physical assistance by guiding their patient's limb to teach a desired movement. In this scenario, a key aspect is the compliance of the interaction, as the therapist can provide subtle cues or impose a movement as demonstration. One approach to studying these interactions involves haptically connecting two individuals through robotic interfaces. Upper-limb studies have shown that pairs of connected individuals estimate one another's goals during tracking tasks by exchanging haptic information, resulting in improved performance dependent on the ability of one's partner and the stiffness of the virtual connection. In this study, our goal was to investigate whether these findings generalize to the lower limb during an ankle tracking task. Pairs of healthy participants (i.e., dyads) independently tracked target trajectories with and without connections rendered between two ankle robots. We tested the effects of connection stiffness as well as visual noise to manipulate the correlation of tracking errors between partners. In our analysis, we compared changes in task performance across conditions while tracking with and without the connection. We found that tracking improvements while connected increased with connection stiffness, favoring the worse partner in the dyad during hard connections. We modeled the interaction as three springs in series, considering the stiffness of the connection and each partners' ankle, to show that improvements were likely due to a cancellation of random tracking errors between partners. These results suggest a simplified mechanism of improvements compared to what has been reported during upper-limb dyadic tracking.

Can we manipulate brain connectivity? A systematic review of cortico-cortical paired associative stimulation effects.

OBJECTIVE: Cortico-cortical paired associative stimulation (ccPAS) is a form of dual-site transcranial magnetic stimulation (TMS) entailing a series of single-TMS pulses paired at specific interstimulus intervals (ISI) delivered to distant cortical areas. The goal of this article is to systematically review its efficacy in inducing plasticity in humans focusing on stimulation parameters and hypotheses of underlying neurophysiology. METHODS: A systematic review of the literature from 2009-2023 was undertaken to identify all articles utilizing ccPAS to study brain plasticity and connectivity. Six electronic databases were searched and included. RESULTS: 32 studies were identified. The studies targeted connections within the same hemisphere or between hemispheres. 28 ccPAS studies were in healthy participants, 1 study in schizophrenia, and 1 in Alzheimer's disease (AD) patients. 2 additional studies used cortico-cortical repetitive paired associative stimulation (cc-rPAS) in generalized anxiety disorder (GAD) patients. Outcome measures include electromyography (EMG), behavioral measures, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). ccPAS seems to be able to modulate brain connectivity depending on the ISI. CONCLUSIONS: ccPAS can be used to modulate corticospinal excitability, brain activity, and behavior. Although the stimulation parameters used across studies reviewed in this paper are varied, ccPAS is a promising approach for basic research and potential clinical applications. SIGNIFICANCE: Recent advances in neuroscience have caused a shift of interest from the study of single areas to a more complex approach focusing on networks of areas that orchestrate brain activity. Consequently, the TMS community is also witnessing a change, with a growing interest in targeting multiple brain areas rather than a single locus, as evidenced by an increasing number of papers using ccPAS. In light of this new enthusiasm for brain connectivity, this review summarizes existing literature and stimulation parameters that have proven effective in changing electrophysiological, behavioral, or neuroimaging-derived measures.