Conductive extracellular matrix derived/chitosan methacrylate/ graphene oxide-pegylated hybrid hydrogel for cell expansion.

Electrical stimulation has emerged as a cornerstone technique in the rapidly evolving field of biomedical engineering, particularly within the realms of tissue engineering and regenerative medicine. It facilitates cell growth, proliferation, and differentiation, thereby advancing the development of accurate tissue models and enhancing drug-testing methodologies. Conductive hydrogels, which enable the conduction of microcurrents in 3D in vitro cultures, are central to this advancement. The integration of high-electroconductive nanomaterials, such as graphene oxide (GO), into hydrogels has revolutionized their mechanical and conductivity properties. Here, we introduce a novel electrostimulation assay utilizing a hybrid hydrogel composed of methacryloyl-modified small intestine submucosa (SIS) dECM (SISMA), chitosan methacrylate (ChiMA), and GO-polyethylene glycol (GO-PEG) in a 3D in vitro culture within a hypoxic environment of umbilical cord blood cells (UCBCs). Results not only demonstrate significant cell proliferation within 3D constructs exposed to microcurrents and early growth factors but also highlight the hybrid hydrogel's physiochemical prowess through comprehensive rheological, morphological, and conductivity analyses. Further experiments will focus on identifying the regulatory pathways of cells subjected to electrical stimulation.

Electro-stimulation modulates syntrophic interactions in methanogenic toluene-degrading microbiota for enhanced functionality.

Syntrophy achieved via microbial cooperation is vital for anaerobic hydrocarbon degradation and methanogenesis. However, limited understanding of the metabolic division of labor and electronic interactions in electro-stimulated microbiota has impeded the development of enhanced biotechnologies for degrading hydrocarbons to methane. Here, compared to the non-electro-stimulated methanogenic toluene-degrading microbiota, electro-stimulation at 800 mV promoted toluene degradation and methane production efficiencies by 11.49 %-14.76 % and 75.58 %-290.11 %, respectively. Hydrocarbon-degrading gene bamA amplification and metagenomic sequencing analyses revealed that f_Syntrophobacteraceae MAG116 may act as a toluene degrader in the non-electro-stimulated microbiota, which was proposed to establish electron syntrophy with the acetoclastic methanogen Methanosarcina spp. (or Methanothrix sp.) through e-pili or shared acetate. In the electro-stimulated microbiota, 37.22 ± 4.33 % of Desulfoprunum sp. (affiliated f_Desulfurivibrionaceae MAG10) and 58.82 ± 3.74 % of the hydrogenotrophic methanogen Methanobacterium sp. MAG74 were specifically recruited to the anode and cathode, respectively. The potential electrogen f_Desulfurivibrionaceae MAG10 engaged in interspecies electron transfer with both syntroph f_Syntrophobacteraceae MAG116 and the anode, which might be facilitated by c-type cytochromes (e.g., ImcH, OmcT, and PilZ). Moreover, upon capturing electrons from the external circuit, the hydrogen-producing electrotroph Aminidesulfovibrio sp. MAG60 could share electrons and hydrogen with the methanogen Methanobacterium sp. MAG74, which uniquely harbored hydrogenase genes ehaA-R and ehbA-P. This study elucidates the microbial interaction mechanisms underlying the enhanced metabolic efficiency of the electro-stimulated methanogenic toluene-degrading microbiota, and emphasizes the significance of metabolic and electron syntrophic interactions in maintaining the stability of microbial community functionality.

Dual electro-/pH-responsive nanoparticle/hydrogel system for controlled delivery of anticancer peptide.

An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.

Muscle preservation in proximal nerve injuries: a current update.

Optimal recovery of muscle function after proximal nerve injuries remains a complex and challenging problem. After a nerve injury, alterations in the affected muscles lead to atrophy, and later degeneration and replacement by fat-fibrous tissues. At present, several different strategies for the preservation of skeletal muscle have been reported, including various sets of physical exercises, muscle massage, physical methods (e.g. electrical stimulation, magnetic field and laser stimulation, low-intensity pulsed ultrasound), medicines (e.g. nutrients, natural and chemical agents, anti-inflammatory and antioxidants, hormones, enzymes and enzyme inhibitors), regenerative medicine (e.g. growth factors, stem cells and microbiota) and surgical procedures (e.g. supercharge end-to-side neurotization). The present review will focus on methods that aimed to minimize the damage to muscles after denervation based on our present knowledge.

Enhancing touch sensibility with sensory electrical stimulation and sensory retraining.

A large proportion of stroke survivors suffer from sensory loss, negatively impacting their independence, quality of life, and neurorehabilitation prognosis. Despite the high prevalence of somatosensory impairments, our understanding of somatosensory interventions such as sensory electrical stimulation (SES) in neurorehabilitation is limited. We aimed to study the effectiveness of SES combined with a sensory discrimination task in a well-controlled virtual environment in healthy participants, setting a foundation for its potential application in stroke rehabilitation. We employed electroencephalography (EEG) to gain a better understanding of the underlying neural mechanisms and dynamics associated with sensory training and SES. We conducted a single-session experiment with 26 healthy participants who explored a set of three visually identical virtual textures-haptically rendered by a robotic device and that differed in their spatial period-while physically guided by the robot to identify the odd texture. The experiment consisted of three phases: pre-intervention, intervention, and post-intervention. Half the participants received subthreshold whole-hand SES during the intervention, while the other half received sham stimulation. We evaluated changes in task performance-assessed by the probability of correct responses-before and after intervention and between groups. We also evaluated differences in the exploration behavior, e.g., scanning speed. EEG was employed to examine the effects of the intervention on brain activity, particularly in the alpha frequency band (8-13 Hz) associated with sensory processing. We found that participants in the SES group improved their task performance after intervention and their scanning speed during and after intervention, while the sham group did not improve their task performance. However, the differences in task performance improvements between groups only approached significance. Furthermore, we found that alpha power was sensitive to the effects of SES; participants in the stimulation group exhibited enhanced brain signals associated with improved touch sensitivity likely due to the effects of SES on the central nervous system, while the increase in alpha power for the sham group was less pronounced. Our findings suggest that SES enhances texture discrimination after training and has a positive effect on sensory-related brain areas. Further research involving brain-injured patients is needed to confirm the potential benefit of our solution in neurorehabilitation.

Regulating microbial redox reactions towards enhanced removal of refractory organic nitrogen from wastewater.

Biotechnology for wastewater treatment is mainstream and effective depending upon microbial redox reactions to eliminate diverse contaminants and ensure aquatic ecological health. However, refractory organic nitrogen compounds (RONCs, e.g., nitro-, azo-, amide-, and N-heterocyclic compounds) with complex structures and high toxicity inhibit microbial metabolic activity and limit the transformation of organic nitrogen to inorganic nitrogen. This will eventually result in non-compliance with nitrogen discharge standards. Numerous efforts suggested that applying exogenous electron donors or acceptors, such as solid electrodes (electrostimulation) and limited oxygen (micro-aeration), could potentially regulate microbial redox reactions and catabolic pathways, and facilitate the biotransformation of RONCs. This review provides comprehensive insights into the microbial regulation mechanisms and applications of electrostimulation and micro-aeration strategies to accelerate the biotransformation of RONCs to organic amine (amination) and inorganic ammonia (ammonification), respectively. Furthermore, a promising approach involving in-situ hybrid anaerobic biological units, coupled with electrostimulation and micro-aeration, is proposed towards engineering applications. Finally, employing cutting-edge methods including multi-omics analysis, data science driven machine learning, technology-economic analysis, and life-cycle assessment would contribute to optimizing the process design and engineering implementation. This review offers a fundamental understanding and inspiration for novel research in the enhanced biotechnology towards RONCs elimination.

Improvement of diffusion tensor imaging-based tractography by free-water correction in nonedematous gliomas: assessment with brain mapping.

OBJECTIVE: The free-water correction algorithm (Freewater Estimator Using Interpolated Initialization [FERNET]) can be applied to standard diffusion tensor imaging (DTI) tractography to improve visualization of subcortical bundles in the peritumoral area of highly edematous brain tumors. Interest in its use for presurgical planning in purely infiltrative gliomas without peritumoral edema has never been evaluated. Using subcortical maps obtained with direct electrostimulation (DES) in awake surgery as a reference standard, the authors sought to 1) assess the accuracy of preoperative DTI-based tractography with FERNET in a series of nonedematous glioma patients, and 2) determine its potential usefulness in presurgical planning. METHODS: Based on DES-induced functional disturbances and tumor topography, the authors retrospectively reconstructed the putatively stimulated bundles and the peritumoral tracts of interest (various associative and projection pathways) of 12 patients. The tractography data obtained with and without FERNET were compared. RESULTS: The authors identified 21 putative tracts from 24 stimulation sites and reconstituted 49 tracts of interest. The number of streamlines of the putative tracts crossing the DES area was 26.8% higher (96.04 vs 75.75, p = 0.016) and their volume 20.4% higher (13.99 cm3 vs 11.62 cm3, p < 0.0001) with FERNET than with standard DTI. Additionally, the volume of the tracts of interest was 22.1% higher (9.69 cm3 vs 7.93 cm3, p < 0.0001). CONCLUSIONS: Free-water correction significantly increased the anatomical plausibility of the stimulated fascicles and the volume of tracts of interest in the peritumoral area of purely infiltrative nonedematous gliomas. Because of the functional importance of the peritumoral zone, applying FERNET to DTI could have potential implications on surgical planning and the safety of glioma resection.

Improving the efficiency of estrus synchronization in cows.

Objective: This study aimed to determine the effects of biologically active substances and electrical stimulation of the uterus in cows on the effectiveness of estrus synchronization. Materials and Methods: Ninety (n = 90) Kazakh white-headed cows were synchronized with two injections of gonadotropin-releasing hormone on days 0 and 9 and prostaglandin F2α on day 7. The cows were divided into six groups and, during the protocol, treated with biologically active substances (Tetramag, Selevetum, antiseptic-stimulator Dorogov 2 fraction, groups 2, 3, and 4). Cows in groups 5 and 6 were treated with the same substances but additionally had electrical stimulation of the uterus, while cows in group 1 were left untreated and served as a control. Results: The results have shown that on Day 0, no differences were observed in E2 concentrations between the groups. However, on the 10th day, a significant disparity was noted in the E2 level among cows in group 6 compared to groups 2, 3, 4, and the control group. Conversely, no significant differences were observed between groups 5 and 6. Likewise, the fertility rate in cows from group 6 was significantly higher compared to groups 2, 3, 4, and the control group, with no significant differences between groups 5 and 6. Conclusion: It can be concluded that the utilization of electrical stimulation of the uterus and the inclusion of certain biological substances during the estrus synchronization protocol demonstrate a positive effect on the reproductive performance of beef cattle in Kazakhstan.

Wireless electrostimulation for cancer treatment: An integrated nanoparticle/coaxial fiber mesh platform.

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.

Germination and stress tolerance of oats treated with pulsed electric field at different phases of seedling growth.

This study explores the impact of pulsed electric field (PEF) application on oat seedling growth and stress tolerance. PEF treatment (99 monopolar, rectangular pulses lasting 10 µs each, with a frequency of 13 Hz and a nominal electric field strength of 2250 V/cm) was applied at two growth stages: (i) when the seedlings had 0.2 cm roots emerging from the kernel, and (ii) when they had a 0.4 cm shoot emerging from the kernel. Post-treatment, the seedlings were hydroponically grown for 8 days. To induce stress, the hydroponic medium was augmented with PEG (15 %) to induce drought stress and NaCl (150 mM) to induce salinity stress. Results demonstrate that applying PEF improved the growth of the root and shoot of oat seedlings. This effect was more pronounced when applied to more developed seedlings. When PEF was applied during the later stage of germination, seedlings exposed to salinity stress showed enhanced shoot growth compared to the control. Under the studied conditions, the application of PEF had no impact on the growth of seedlings under drought stress.

Effectiveness and Safety of Non-Invasive Neuromodulation for Vision Restoration: A Systematic Review and Meta-Analysis.

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency.

Mortality and Costs of Cardiac Implantable Electronic Device (CIED) Infections According to the Therapeutic Approach: A Single-Center Cohort Study.

Background: Cardiac device infections are serious adverse events associated with considerable morbidity and mortality, significant costs, and increased healthcare utilization. The aim of this study is to calculate the costs of treatment of cardiac implantable electrostimulation device (CIED)-related infections for different types of infection (local or systemic) and therapeutic approaches. Patients and Methods: Single-center cohort (1985-2018). The costs of the CIED-related infections were analyzed according to initial treatment (antimicrobial treatment exclusively, local approach, or transvenous lead extraction (TLE)). Total costs (including those for hospitalization stay, drugs, extraction material, and newly implanted devices) were assigned to each case until its final resolution. Results: A total of 380 cases (233 local and 147 systemic infections) were analyzed. The average cost of systemic infection was EUR 34,086, mainly due to hospitalization (78.5%; mean: 24 ± 14 days), with a mortality rate of 10.8%. Local infection had a mortality rate of 2.5% (mainly related to the extraction procedure) and an average cost of EUR 21,790, which was higher in patients with resynchronization therapy devices and defibrillators (46% of total costs). Surgical procedures limited to the pocket for local infections resulted in a high rate of recurrence (87%), evolved to systemic infections in 48 patients, and had a higher cost compared to TLE (EUR 42,978 vs. EUR 24,699; p < 0.01). Conclusions: The costs of treating CIED-related infections are high and mainly related to the type of treatment and length of hospitalization. Complete device removal is always the most effective approach and is a cost-saving strategy.

Comparative Analysis of Psychophysiological Responses in Fibromyalgia Patients: Evaluating Neuromodulation Alone, Neuromodulation Combined with Virtual Reality, and Exercise Interventions.

BACKGROUND AND OBJECTIVES: Fibromyalgia, a chronic condition, manifests as widespread musculoskeletal pain, fatigue, sleep disturbances, autonomic and cognitive dysfunction, hypersensitivity to stimuli, and various somatic and psychiatric symptoms. This study, a controlled and randomized experiment, aimed to evaluate and compare the immediate effects of different treatments on fibromyalgia patients. MATERIALS AND METHODS: The treatments included the EXOPULSE Mollii suit, a combination of the EXOPULSE Mollii suit with a virtual reality (VR) protocol, and a physical exercise regimen. A cohort of 89 female fibromyalgia patients was randomly assigned to one of four groups: Control (n = 20), Suit only (n = 22), Suit combined with VR (n = 21), and Exercise (n = 26). RESULTS: This study found notable differences across the groups in several key parameters. In the Control group, significant changes were observed in Forced Expiratory Volume (FEV 1/FEV 6), the Numeric Rating Scale (NRS) for pain, Pressure Pain Threshold (PPT) at the epicondyle, cortical arousal levels, the 10 m up-and-go test, and in all measured variables related to temperature and muscle oxygenation. For the group using the suit alone, there were significant differences noted in the NRS, the chair stand test, palm temperature, and all muscle oxygenation parameters. The Suit + VR group showed significant changes in the NRS, PPT at the knee, handgrip strength test, the 10 m up-and-go test, one-leg balance test with the right leg, muscle oxygen saturation (SmO2), deoxygenated hemoglobin (HHb), and oxygenated hemoglobin (O2Hb). Finally, the Exercise group exhibited significant differences in FEV 1/FEV 6, chest perimeter difference, NRS, PPT at both the epicondyle and knee, cortical arousal, the chair stand test, the 10-m up-and-go test, and in SmO2, HHb, and O2Hb levels. CONCLUSIONS: combining neuromodulation with VR and targeted exercise regimens can effectively alleviate fibromyalgia symptoms, offering promising avenues for non-pharmacological management.

Non-Athletic Cohorts Enrolled in Longitudinal Whole-Body Electromyostimulation Trials-An Evidence Map.

Whole-body electromyostimulation (WB-EMS) can be considered as a time-efficient, joint-friendly, and highly customizable training technology that attracts a wide range of users. The present evidence map aims to provide an overview of different non-athletic cohorts addressed in WB-EMS research. Based on a comprehensive systematic search according to PRISMA, eighty-six eligible longitudinal trials were identified that correspond with our eligibility criteria. In summary, WB-EMS research sufficiently covers all adult age categories in males and females. Most cohorts addressed (58%) were predominately or exclusively overweight/obese, and in about 60% of them, diseases or conditions were inclusion criteria for the trials. Cohorts specifically enrolled in WB-EMS trials suffer from cancer/neoplasm (n = 7), obesity (n = 6), diabetes mellitus (n = 5), metabolic syndrome (n = 2), nervous system diseases (n = 2), chronic heart failure (n = 4), stroke (n = 1), peripheral arterial diseases (n = 2), knee arthrosis (n = 1), sarcopenia (n = 3), chronic unspecific low back pain (n = 4), and osteopenia (n = 3). Chronic kidney disease was an eligibility criterion in five WB-EMS trials. Finally, three studies included only critically ill patients, and two further studies considered frailty as an inclusion criterion. Of importance, no adverse effects of the WB-EMS intervention were reported. In summary, the evidence gaps in WB-EMS research were particular evident for cohorts with diseases of the nervous and cerebrovascular system.

Electroacupuncture Reduces Inflammatory Bowel Disease in Obese Mice by Activating the Nrf2/HO-1 Signaling Pathways and Repairing the Intestinal Barrier.

Background: Electroacupuncture (EA) is used to treat inflammatory bowel disease (IBD). Nevertheless, the precise mechanisms by which this approach safeguards against obesity-induced intestinal barrier damage has not been fully understood. Objective: This study aimed to assess whether EA could ameliorate intestinal barrier damage that had been reversed in a mouse model of obesity induced by a high-fat diet (HFD) and whether this repair is correlated with ferroptosis and gut microbiota enhancement. Methods: To assess the potential of EA to prevent obesity and restore the intestinal barrier, we divided in C57BL/6J mice into two groups; one was fed with HFD and another one with a normal diet. Samples of stool, blood, fat, and intestinal epithelium were then evaluated, along with body weight. Results: Following EA, we observed a significant reduction in body weight, fat accumulation, and serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels; an increase was seen in high-density lipoprotein cholesterol (HDL-C) levels. EA also activated the Nrf2 signaling pathway; upregulated the expression of GPX4, FTH1, and SLC7A11; and downregulated the expression of TFR1. In addition, the administration of EA resulted in a notable modification of the gut microbiota composition, characterized by a decrease in the Firmicutes to Bacteroidetes ratio. Conclusion: EA had beneficial effects on weight loss and showed potential ability to repair the intestinal barrier by activating the Nrf2 signaling pathway, inhibiting intestinal inflammation and ferroptosis, and regulating the intestinal microbiota to treat IBD caused by HFD-induced obesity.

Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Should I stay or should I go? The cerebral bases of street-crossing decision.

An observer willing to cross a street must first estimate if the approaching cars offer enough time to safely complete the task. The brain areas supporting this perception, known as Time-To-Contact (TTC) perception, have been mainly studied through noninvasive correlational approaches. We carried out an experiment in which patients were tested during an awake brain surgery electrostimulation mapping to examine the causal implication of various brain areas in the street-crossing decision process. Forty patients were tested in a gap acceptance task before their surgery to establish a baseline performance. The task was individually adapted upon this baseline level and carried out during their surgery. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. A total of 103 stimulation sites were tested, allowing to establish a large map of the areas involved in the street-crossing decision. Multiple sites were found to impact the gap acceptance decision. A direct implication was however found mostly for sites within the right parietal lobe, while indirect implication was found for sites within the language, motor, or attentional networks. The right parietal lobe can be considered as causally influencing the gap acceptance decision. Other positive sites were all accompanied with dysfunction in other cognitive functions, and therefore should probably not be considered as the site of TTC estimation.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

Peripheral fatigue regulation during knee extensor exercise in type 1 diabetes and consequences on the force-duration relationship.

PURPOSE: This study aimed to examine if peripheral fatigue is adjusted during knee extensor (KE) exercise in order not to surpass a critical threshold patient with type 1 diabetes (T1D) and the consequences of this mechanism on the force-duration relationship. METHODS: Eleven T1D individuals randomly performed two different sessions in which they performed 60 maximum voluntary contractions (MVC; 3 s contraction, 2 s relaxation). One trial was performed in the non-fatigued state (CTRL) and another after fatiguing neuromuscular stimulation of the KE (FNMES). Peripheral and central fatigue were quantified by the difference between pre and post exercise in quadriceps voluntary activation (ΔVA) and potentiated twitch (ΔPtw). Critical torque (CT) was determined as the average force of the last 12 contractions, whereas W' was calculated as the area above the CT. RESULTS: Although FNMES led to a significant decrease in potentiated twitch (Ptw) before performing the 60-MVCs protocol (p < 0.05), ΔVA (∼ -7.5%), ΔPtw (∼ -39%), and CT (∼816 N) post-MVCs were similar between the two conditions. The difference in W' between CTRL and FNMES was correlated with the level of pre-fatigue induced in FNMES (r2 = 0.60). In addition, W' was correlated with ΔPtw (r2 = 0.62) in the CTRL session. CONCLUSION: Correlative results in the present study indicate that regulating peripheral fatigue mechanisms at a critical threshold limit W'. Additionally, peripheral fatigue during KE exercise is limited to an individual threshold in T1D patients.