Preserved neural dynamics across animals performing similar behaviour.

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.

Replication of a neuroimaging biomarker for striatal dysfunction in psychosis.

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n = 101) from healthy controls (n = 51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n = 97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC = 75.4%, 95% CI = 67.0-83.3%; in non-affective psychosis AUC = 80.5%, 95% CI = 72.1-88.0%, and in affective psychosis AUC = 58.7%, 95% CI = 44.2-72.0%). Test-retest reliability ranged between ICC = 0.48 (95% CI = 0.35-0.59) and ICC = 0.22 (95% CI = 0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC = 0.51 (95% CI = 0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 min, diagnostic classification of the FSA increased from AUC = 71.7% (95% CI = 63.1-80.3%) to 75.4% (95% CI = 67.0-83.3%) and phase encoding direction reliability from ICC = 0.29 (95% CI = 0.14-0.43) to ICC = 0.51 (95% CI = 0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.

Improved cognition after rifaximin treatment is associated with changes in intra- and inter-brain network functional connectivity.

BACKGROUND: Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well. METHODS: Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed. RESULTS: After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers. CONCLUSIONS: There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.

Lattice defects induced by microtubule-stabilizing agents exert a long-range effect on microtubule growth by promoting catastrophes.

Microtubules are dynamic cytoskeletal polymers that spontaneously switch between phases of growth and shrinkage. The probability of transitioning from growth to shrinkage, termed catastrophe, increases with microtubule age, but the underlying mechanisms are poorly understood. Here, we set out to test whether microtubule lattice defects formed during polymerization can affect growth at the plus end. To generate microtubules with lattice defects, we used microtubule-stabilizing agents that promote formation of polymers with different protofilament numbers. By employing different agents during nucleation of stable microtubule seeds and the subsequent polymerization phase, we could reproducibly induce switches in protofilament number and induce stable lattice defects. Such drug-induced defects led to frequent catastrophes, which were not observed when microtubules were grown in the same conditions but without a protofilament number mismatch. Microtubule severing at the site of the defect was sufficient to suppress catastrophes. We conclude that structural defects within the microtubule lattice can exert effects that can propagate over long distances and affect the dynamic state of the microtubule end.

Modelling Asphalt Overlay As-Built Roughness Based on Profile Transformation-Case for Paver Using Automatic Levelling System.

The as-built roughness, or smoothness obtained during pavement construction, plays an important role in road engineering since it serves as an indicator for both the level of service provided to users and the overall standard of construction quality. Being able to predict as-built roughness is therefore important for supporting pavement design and management decision making. An as-built IRI prediction model for asphalt overlays based on profile transformation was proposed in a previous study. The model, used as basis for this work, was developed for the case of wheeled pavers without automatic screed levelling. This study presents further development of the base prediction model, including the use of an automatic screed control system through a long-distance averaging mobile reference. Formulation of linear systems that constitute the model are presented for the case of a wheeled paver using contactless acoustic sensors set-up over a floating levelling beam attached to the paver. To calibrate the model, longitudinal profile data from the Long-Term Pavement Performance SPS-5 experiment was used, obtaining a mean error of 0.17 m/km for the predicted IRI. The results obtained demonstrate the potential of the proposed approach as a modelling alternative.

Development of Self-Sensing Asphalt Pavements: Review and Perspectives.

The digitalization of the road transport sector necessitates the exploration of new sensing technologies that are cost-effective, high-performing, and durable. Traditional sensing systems suffer from limitations, including incompatibility with asphalt mixtures and low durability. To address these challenges, the development of self-sensing asphalt pavements has emerged as a promising solution. These pavements are composed of stimuli-responsive materials capable of exhibiting changes in their electrical properties in response to external stimuli such as strain, damage, temperature, and humidity. Self-sensing asphalt pavements have numerous applications, including in relation to structural health monitoring (SHM), traffic monitoring, Digital Twins (DT), and Vehicle-to-Infrastructure Communication (V2I) tools. This paper serves as a foundation for the advancement of self-sensing asphalt pavements by providing a comprehensive review of the underlying principles, the composition of asphalt-based self-sensing materials, laboratory assessment techniques, and the full-scale implementation of this innovative technology.

Effects of phase encoding direction on test-retest reliability of human functional connectome.

The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction (PED). However, whether and how PED would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of PED on global, nodal, and edge connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by PED were consistently mapped to the cingulate cortex, temporal lobe, sensorimotor areas, and visual areas, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Better ICCs were also observed during PA scans at the edge level, in particular when global signal regression (GSR) was not performed. Further, we demonstrated that the observed reliability differences between PEDs may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could increase median ICCs, especially at the nodal and edge levels. Similar results at the global and nodal levels were replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that PED has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention.

Maternal and perinatal outcomes in mixed antenatal care modality implementing telemedicine in the southwestern region of Colombia during the COVID-19 pandemic.

INTRODUCTION: Contingency measures due to the COVID-19 pandemic limited access to routine prenatal care for pregnant women, increasing the risk of pregnancy complications due to poor prenatal follow-up, especially in those patients at high obstetric risk. This prompted the implementation and adaptation of telemedicine. OBJECTIVE: We aim to evaluate the maternal and perinatal outcomes of patients who received prenatal care in-person and by telemedicine. METHODS: We conducted a retrospective observational cohort study of pregnant women who received exclusive in-person and alternate (telemedicine and in-person) care from March to December 20,202, determining each group's maternal and neonatal outcomes. RESULTS: A total of 1078 patients were included, 156 in the mixed group and 922 in the in-person group. The patients in the mixed group had a higher number of prenatal controls (8 (6-9) vs 6 (4-8) p < 0.001), with an earlier gestational age at onset (7.1 (6-8.5) vs 9.3 (6.6-20.3), p < 0.001), however, they required a longer hospital stay (26 (16,67%) vs 86 (9,33%), p = 0.002) compared to those attended in-person; there were no significant differences in the development of obstetric emergencies, maternal death or neonatal complications. DISCUSSION: Incorporating telemedicine mixed with in-person care could be considered as an alternative for antenatal follow-up of pregnant women in low- and middle-income countries with barriers to timely and quality health care access.

Accelerated Ray Launching Method for Efficient Field Coverage Studies in Wide Urban Areas.

The implementation of a fast and efficient computer tool for field coverage studies in urban mobile radio systems is presented in this work. An accelerated and tailored ray launching method takes advantage of a ray tracing programmable framework optimized for massively parallel processing on GPUs. The PlotOptiX API is used to customize the code before applying the electromagnetic equations. The proposed code is described, and results are shown to demonstrate its correct operation. A high number of diffractions and reflections can be tracked in each ray from the transmitter to the receiver. In addition to the typical point-to-point simulation, measurement planes can also be set as receivers to provide fast predictions in wide urban areas.

Thermoelectric Enhancement in Single Organic Radical Molecules.

Organic thermoelectric materials have potential for wearable heating, cooling, and energy generation devices at room temperature. For this to be technologically viable, high-conductance (G) and high-Seebeck-coefficient (S) materials are needed. For most semiconductors, the increase in S is accompanied by a decrease in G. Here, using a combined experimental and theoretical investigation, we demonstrate that a simultaneous enhancement of S and G can be achieved in single organic radical molecules, thanks to their intrinsic spin state. A counterintuitive quantum interference (QI) effect is also observed in stable Blatter radical molecules, where constructive QI occurs for a meta-connected radical, leading to further enhancement of thermoelectric properties. Compared to an analogous closed-shell molecule, the power factor is enhanced by more than 1 order of magnitude in radicals. These results open a new avenue for the development of organic thermoelectric materials operating at room temperature.

Dislocation and survival rate of dual mobility cups in revision total hip arthroplasty in patients with high risk of instability.

PURPOSE: Instability remains as an unsolved complication after revision total hip arthroplasty (rTHA). Dual mobility (DM) cups have decreased dislocation rate in rTHA; however, there are few clinical studies that evaluate the risk of dislocation after rTHA in patients with high risk of instability. METHODS: Between 2007 and 2019, 95 consecutive rTHA using a DM cup, in 93 patients with instability risk factors were retrospectively reviewed. Instability risk factors were defined as follows: deficient abductor mechanism (22.1%), previous dislocation (68.4%), Paprosky 3 acetabular bone defect (21.1%), neuromuscular disease (4.2%), lumbar spine arthrodesis (6.3%), and more than one previous surgery (33.6%). Mean follow-up was 4.3 ± 2.4 years. Clinical and radiographic parameters were reported. DM cup survival was determined using a Kaplan-Meier analysis with re-revision for any cause as the end-point. Surgical complications and re-dislocation rate was recorded. RESULTS: Seven DM cups were re-revised; three due to aseptic loosening, three due to peri-prosthetic joint infection (PJI), and one due to instability. At seven years follow-up, the survival rate of the DM cup using re-revision for any reason as the end-point was 82.4% (95% confidence interval, 66.4-98.4%). There were 12 (12.6%) complications: two (2.1%) dislocations, six (6.3%) PJI, four (4.2%) peri-prosthetic fractures. CONCLUSION: Our findings suggest DM cups are effective reducing dislocation rate in rTHA in patients with a high risk of instability, without increasing early aseptic loosening and with a low rate of dislocation. Nevertheless, longer follow-up is needed to confirm implant stability and dislocation rates in the long term.

Neurofilament Light Chain Protein in Plasma and Extracellular Vesicles Is Associated with Minimal Hepatic Encephalopathy and Responses to Rifaximin Treatment in Cirrhotic Patients.

Neurofilament light chain protein (NfL) levels reflect neuronal damage in several neurological diseases and have been proposed as a possible biomarker. Plasma extracellular vesicles (EVs) could play an important role as mediators of the inflammatory changes associated with inducing minimal hepatic encephalopathy (MHE) in cirrhotic patients. This study investigated the association of NfL levels in plasma and EVs with the presence of MHE in cirrhotic patients, and with responses to rifaximin treatment. The NfL levels in plasma and EVs were assessed in 71 patients with liver cirrhosis (40 with MHE and 31 without MHE) and 26 controls. A total of 31 patients with MHE received rifaximin treatment. We examined changes in NfL levels in plasma and EVs before and after 6 months of rifaximin treatment. The NfL measures were correlated with cognitive alterations and plasma inflammatory cytokines. MHE patients showed increased plasma levels of NfL, which were reverted after rifaximin treatment in patients who responded to treatment. The NfL content in EVs also showed a reversal pattern in MHE patients treated with rifaximin. In multivariable analyses, NfL levels were independently associated with the presence of MHE. We also showed that patients with high levels of both ammonia and fractalkine had significantly higher NfL levels than patients with low levels of least one of these parameters. Rifaximin treatment in MHE patients showed promising results in improving axonal damage, suggesting that rifaximin may have therapeutic benefits against disease progression in MHE.

Mild Cognitive Impairment Is Associated with Enhanced Activation of Th17 Lymphocytes in Non-Alcoholic Fatty Liver Disease.

Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The mechanisms involved remain unclear. The plasma concentrations of several cytokines and chemokines were measured in 71 NAFLD patients (20 with and 51 without MCI) and 61 controls. Characterization and activation of leukocyte populations and CD4+ sub-populations were carried out and analyzed by flow cytometry. We analyzed the cytokines released from CD4+ cell cultures and the mRNA expression of transcription factors and receptors in peripheral blood mononuclear cells. The appearance of MCI in NAFLD patients was associated with increased activation of CD4+ T lymphocytes, mainly of the Th17 subtype, increased plasma levels of pro-inflammatory and anti-inflammatory cytokines such as IL-17A, IL-23, IL-21, IL-22, IL-6, INF-γ, and IL-13, and higher expression of the CCR2 receptor. Constitutive expression of IL-17 was found in cultures of CD4+ cells from MCI patients, reflecting Th17 activation. High IL-13 plasma levels were predictive of MCI and could reflect a compensatory anti-inflammatory response to the increased expression of pro-inflammatory cytokines. This study identified some specific alterations of the immune system associated with the appearance of neurological alterations in MCI patients with NAFLD that could be the basis to improve and restore cognitive functions and quality of life in these patients.

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches.

Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described. The molecular structures of several intermediates and DHPs were elucidated by X-ray single-crystal diffraction. Molecular properties and switching capabilities of both types of DHPs were assessed by light irradiation experiments, spectroelectrochemistry, and cyclic voltammetry. Spectroelectrochemistry, in combination with density functional theory (DFT) calculations, shows reversible electrochemical switching from the DHP forms to the cyclophanediene (CPD) forms. Charge-transport behavior was assessed in single-molecule scanning tunneling microscope (STM) break junctions, combined with density functional theory-based quantum transport calculations. All DHPs with surface-contacting groups form stable molecular junctions. Experiments show that the molecular conductance depends on the substitution pattern of the DHP motif. The conductance was found to decrease with increasing applied bias.

Price elasticity of demand for voluntary health insurance plans in Colombia.

BACKGROUND: Since 1993, Colombia has had a mandatory social health insurance scheme that aims to provide universal health coverage to all citizens. However, some contributory regime participants purchase voluntary private health insurance (VPHI) to access better quality health services (i. e., physicians and hospitals), shorter waiting times, and a more extensive providers' network. This article aims to estimate the price elasticity of demand for the VPHI market in Colombia. METHODS: We use data from the 2016-2017 consumer expenditure national survey and apply a Heckman selection model to address the selection problem into purchasing private insurance. Using the estimation results to further estimate the price semi-elasticity for VPHI, we then calculate the price elasticity for the households' health expenditure and acquisition of VHPI. RESULTS: Our main findings indicate that a 1% VPHI price increase reduces the proportion of households affiliated to a VPHI in the country by about 2.32% to 4.66%, with robust results across sample restrictions. There are relevant differences across age groups, with younger households' heads being less responsive to VPHI price changes. CONCLUSIONS: We conclude that the VPHI demand in Colombia is noticeably elastic, and therefore tax policy changes can have a significant impact on public health insurance expenditures. The government should estimate the optimal VPHI purchase in order to reduce any welfare loss that the current arrangement might be generating.

Arthroscopic surgery versus open surgery for lateral epicondylitis in an active work population: a comparative study.

BACKGROUND: Lateral epicondylitis is common in workers who perform repetitive movements of the entire upper limb. Approximately 85%-90% of patients respond satisfactorily to conservative treatment, but in resistant patients, surgical treatment is considered. Classic open surgery is successful in between 70% and 97% of patients, similarly to more modern techniques such as arthroscopy. We sought to demonstrate the superiority of the Wolff technique in terms of clinical results. The goals of this study were to compare the functional and pain outcomes of arthroscopic surgery with open surgery using fasciotomy via the Wolff technique in the treatment of lateral epicondylitis. METHODS: This was a retrospective study of 47 working-age patients with resistant lateral epicondylitis: 27 underwent arthroscopic surgery and 20 underwent open surgery. Visual analog scale scores for pain and function, as well as the QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score, Mayo Elbow Performance Score, and Broberg and Morrey Rating System score, were collected preoperatively and postoperatively; return to patients' previous work and surgical time were also recorded. RESULTS: No statistically significant differences were observed between the groups in the reduction in the visual analog scale score (5.26 in arthroscopy group vs. 5.75 in fasciotomy group, P = .5), QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score (19 vs. 19.4, P = .9), Mayo Elbow Performance Score (82 vs. 81.5, P = .8), or Broberg and Morrey Rating System score (81.9 vs. 82.6, P = .9). The differences in terms of time off were also not statistically significant. The period of work leave corresponded, on average, to 83.78 days in the arthroscopy group and 89.95 days in the Wolff group. The mean surgical time was 44.2 minutes in the group undergoing arthroscopic intervention and 27.5 minutes in the fasciotomy group, showing a statistically significant difference (P < .001). CONCLUSIONS: Arthroscopic surgery and open surgery provide similar functional results and pain reduction in the treatment of lateral epicondylitis.

An Ultrasonic Tomography System for the Inspection of Columns in Architectural Heritage.

A new versatile and geometrically reconfigurable ultrasonic tomography system (UTS) has been designed to inspect and obtain information about the internal structure and inner damage of columns in heritage buildings. This nondestructive system is considered innovative because it aims to overcome common limitations of existing systems. Tomographic inspections are typically carried out manually and are thus limited to small portions of construction elements. The proposed UTS allows the automatization of the inspection and the generation of numerous tomographic slices along the height of the column. It is valid for multiple types of columns and materials. In the present work, the system was tested on two limestone columns of the north façade of the Convent of Carmo in Lisbon, Portugal. The UTS is composed of a mechanical and an electronic system. The mechanical system consists of four linear motion subsystems mounted in a square setup. A transducer is placed on each of the axes, acting as emitter or receiver of the ultrasonic signals. The mechanical system also includes a guide system to adapt the inspections to the complex geometry of the columns. The electronic system allows the control and the synchronization of the movements and the emission/reception configuration of the four ultrasonic transducers.

Plasma Extracellular Vesicles Play a Role in Immune System Modulation in Minimal Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is associated with changes in the immune system including an increased pro-inflammatory environment and altered differentiation of CD4+ T lymphocytes. The mechanisms remain unknown. Changes in extracellular vesicle (EV) cargo including proteins and miRNAs could play a main role as mediators of immune system changes associated with MHE. The aim was to assess whether plasma EVs from MHE patients played a role in inducing the pro-inflammatory environment and altered differentiation of CD4+ T lymphocyte subtypes in MHE patients. We characterized the miRNA and protein cargo of plasma EVs from 50 cirrhotic patients (27 without and 23 with MHE) and 24 controls. CD4+ T cells from the controls were cultured with plasma EVs from the three groups of study, and the cytokine release and differentiation to CD4+ T-cell subtypes were assessed. Plasma EVs from MHE patients had altered miRNA and protein contents, and were enriched in inflammatory factors compared to the controls and patients without MHE. EVs from MHE patients modulated the expression of pro-inflammatory IL-17, IL-21, and TNF-α and anti-inflammatory TGF-ß in cultured CD4+ T lymphocytes, and increased the proportion of Th follicular and Treg cells and the activation of Th17 cells. In conclusion, plasma EVs could play an important role in the induction of immune changes observed in MHE.

Molecular Structure-(Thermo)electric Property Relationships in Single-Molecule Junctions and Comparisons with Single- and Multiple-Parameter Models.

The most probable single-molecule conductance of each member of a series of 12 conjugated molecular wires, 6 of which contain either a ruthenium or platinum center centrally placed within the backbone, has been determined. The measurement of a small, positive Seebeck coefficient has established that transmission through these molecules takes place by tunneling through the tail of the HOMO resonance near the middle of the HOMO-LUMO gap in each case. Despite the general similarities in the molecular lengths and frontier-orbital compositions, experimental and computationally determined trends in molecular conductance values across this series cannot be satisfactorily explained in terms of commonly discussed "single-parameter" models of junction conductance. Rather, the trends in molecular conductance are better rationalized from consideration of the complete molecular junction, with conductance values well described by transport calculations carried out at the DFT level of theory, on the basis of the Landauer-Büttiker model.