Constant Stimulation Research Articles

Application of biomedical cell products in the treatment of congenital epidermolysis bullosa

Congenital epidermolysis bullosa is a phenotypically and genetically heterogeneous group of genodermatoses, which which is clinically manifested by the development of blisters on the skin and mucous membranes after mechanical injury. The presence of long-term erosive and ulcerative defects in patients with congenital epidermolysis bullosa reduces the quality of patients` life and also leads to malignancy of the lesions, as a result of constant stimulation of regenerative processes.Currently, there are a lot of publications describing the use of skin substitutes, three-dimensional tissue-engineered structures based on auto- and allogeneic cells that promote rapid epithelization of wounds in patients with congenital epidermolysis bullosa. The most prospective and at the same time the least studied direction of congenital epidermolysis bullosa treatment is the use of a combined skin equivalent created on the basis of keratinocytes and fibroblasts, which mixes the advantages of epidermal and dermal grafts.

Why young adults consume media content about serial killers: Evidence from Russia

This article explores Russian young adults’s motives for consuming media content related to serial killers. Based on a sociological perspective of consumption, the research integrates concepts such as consumerism and “new hedonism” postulated by Campbell with Giddens’s structuration theory and Goffman’s stigma theory. We argue that consumerists’ motivations and images of serial killers are products of modernity. A total of 26 semi-structured online interviews were conducted with young adults aged 18–35 years from 14 cities in Russia. We then performed a thematic qualitative analysis using the AtlasTI software. Our findings show that consumers of media content about serial killers have two main categories of motives: cognitive and emotional. Cognitive motives could be viewed through the lens of the need for ontological security, an attempt to study a potential threat. Emotional motives were associated with satisfying the consumerist need for constant emotional stimulation and pleasure. Future studies may focus on classifying audiences based on their motives for consuming serial-killer media content and examining correlations with consumption practices as well as the supply-side motives of producing this type of content.

Levodopa / opicapone as a complement to STN-DBS in clinical practice. A retrospective single-centre analysis.

ObjectiveDeep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment option in Parkinson's disease with motor and non-motor fluctuations allowing for postoperative reduction of dopaminergic medication. However, evidence is scarce on optimal medication adjustments following STN-DBS implantation. Opicapone allows for long-lasting inhibition of the catechol-O-methyltransferase (COMT) thereby enabling more constant dopaminergic stimulation compared to levodopa alone. However, especially COMT inhibitors are regularly discontinued after STN-DBS surgery. In this single-centre retrospective analysis, we aimed to analyse the clinical phenotype of patients selected for opicapone treatment following STN-DBS implantation and to define clinical determinants of patients requiring more intense dopamine-stabilising strategies after STN-DBS implantation. MethodsA patient cohort treated with STN-DBS + levodopa + opicapone (n = 16) was compared to an age-matched control cohort without opicapone treatment at baseline before and ≥ 5 months post-surgery. As main outcomes we assessed the MDS-UPDRS III and IV scores and reduction of the cumulative dopaminergic medication quantified by the levodopa equivalent dosages (LED). ResultsWhilst the MDS-UPDRS III (median [min – max]) in patients with STN-DBS as well as anatomical electrode positions did not differ significantly between the opicapone 20 [4–40] and control cohort 14 [1–44], the patients selected for opicapone treatment showed a significantly higher degree of dyskinesias already preoperatively as reflected by a UPDRS-IV A subscore of 2 [0–4] compared to controls 0 [0–4]. Postoperatively, the opicapone cohort showed stronger motor fluctuations MDS-UPDRS IV 6 [0–14] compared to the controls 0 [0−10], albeit without statistical significance. Moreover, the opicapone cohort showed significantly less reduction of dopaminergic medication (−36.4 % vs. -46.2 % in the control cohort) following STN-DBS implantation independent from the intake of dopamine agonists. ConclusionThese results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.

Immunopathology of lung transplantation: from infection to rejection and vice versa.

Lung transplantation offers a lifesaving option for patients with end-stage lung disease, but it is marred by a high risk of post-transplant infections, particularly involving multidrug-resistant bacteria, Cytomegalovirus, and fungal pathogens. This elevated infection rate, the highest among solid organ transplants, poses a significant challenge for clinicians, particularly within the first year post-transplantation, where infections are the leading cause of mortality. The direct exposure of lung allografts to the external environment exacerbates this vulnerability leading to constant immune stimulation and consequently to an elevated risk of triggering alloimmune responses to the lung allograft. The necessity of prolonged immunosuppression to prevent allograft rejection further complicates patient management by increasing susceptibility to infections and neoplasms, and complicating the differentiation between rejection and infection, which require diametrically opposed management strategies. This review explores the intricate balance between preventing allograft rejection and managing the heightened infection risk in lung transplant recipients.

Single-trial movement intention detection estimation in patients with Parkinson’s disease: a movement-related cortical potential study

Objectives. Parkinson patients often suffer from motor impairments such as tremor and freezing of movement that can be difficult to treat. To unfreeze movement, it has been suggested to provide sensory stimuli. To avoid constant stimulation, episodes with freezing of movement needs to be detected which is a challenge. This can potentially be obtained using a brain–computer interface (BCI) based on movement-related cortical potentials (MRCPs) that are observed in association with the intention to move. The objective in this study was to detect MRCPs from single-trial EEG. Approach. Nine Parkinson patients executed 100 wrist movements and 100 ankle movements while continuous EEG and EMG were recorded. The experiment was repeated in two sessions on separate days. Using temporal, spectral and template matching features, a random forest (RF), linear discriminant analysis, and k-nearest neighbours (kNN) classifier were constructed in offline analysis to discriminate between epochs containing movement-related or idle brain activity to provide an estimation of the performance of a BCI. Three classification scenarios were tested: 1) within-session (using training and testing data from the same session and participant), between-session (using data from the same participant from session one for training and session two for testing), and across-participant (using data from all participants except one for training and testing on the remaining participant). Main results. The within-session classification scenario was associated with the highest classification accuracies which were in the range of 88%–89% with a similar performance across sessions. The performance dropped to 69%–75% and 70%–75% for the between-session and across-participant classification scenario, respectively. The highest classification accuracies were obtained for the RF and kNN classifiers. Significance. The results indicate that it is possible to detect movement intentions in individuals with Parkinson’s disease such that they can operate a BCI which may control the delivery of sensory stimuli to unfreeze movement.

Data-driven dynamic profiles of tonic heat pain perception in pain-free volunteers are associated with differences in anandamide levels

Our laboratory previously developed a method for assessing experimentally induced pain perception through a 2-min constant heat pain stimulation. However, the traditional analysis relying on group means struggles to interpret the considerable inter-individual variability due to the dynamic nature of the response. Recently, trajectory analysis techniques based on extended mixed models have emerged, providing insights into distinct response profiles. Notably, these methods have never been applied to pain paradigms before. Furthermore, various socio-demographic and neurobiological factors, including endocannabinoids, may account for these inter-individual differences. This study aims to apply the novel analysis to dynamic pain responses and investigate variations in response profiles concerning socio-demographic, psychological, and blood endocannabinoid concentrations. 346 pain-free participants were enrolled in a psychophysical test involving a continuous painful heat stimulation lasting for 2 min at a moderate intensity. Pain perception was continuously recorded using a computerized visual scale. Dynamic pain response analyses were conducted using the innovative extended mixed model approach. In contrast to the traditional group-mean analysis, the extended mixed model revealed three pain response trajectories. Trajectory 1 is characterized by a delay peak pain. Trajectory 2 is equivalent to the classic approach (peak pain follow by a constant and moderate increase of pain perception). Trajectory 3 is characterized by extreme responses (steep peak pain, decrease, and increase of pain perception), Furthermore, age and blood anandamide levels exhibited significant variations among these three trajectories. Using an innovative statistical approach, we found that a large proportion of our sample had a response significantly different from the average expected response. Endocannabinoid system seems to play a role in pain response profile.

The neuron as a direct data-driven controller

In the quest to model neuronal function amid gaps in physiological data, a promising strategy is to develop a normative theory that interprets neuronal physiology as optimizing a computational objective. This study extends current normative models, which primarily optimize prediction, by conceptualizing neurons as optimal feedback controllers. We posit that neurons, especially those beyond early sensory areas, steer their environment toward a specific desired state through their output. This environment comprises both synaptically interlinked neurons and external motor sensory feedback loops, enabling neurons to evaluate the effectiveness of their control via synaptic feedback. To model neurons as biologically feasible controllers which implicitly identify loop dynamics, infer latent states, and optimize control we utilize the contemporary direct data-driven control (DD-DC) framework. Our DD-DC neuron model explains various neurophysiological phenomena: the shift from potentiation to depression in spike-timing-dependent plasticity with its asymmetry, the duration and adaptive nature of feedforward and feedback neuronal filters, the imprecision in spike generation under constant stimulation, and the characteristic operational variability and noise in the brain. Our model presents a significant departure from the traditional, feedforward, instant-response McCulloch-Pitts-Rosenblatt neuron, offering a modern, biologically informed fundamental unit for constructing neural networks.

Effect of different electrical stimulation systems on beef quality and palatability: Constant current compared to constant voltage

This study examined the effects of constant current electrical stimulation (CCES) compared to constant voltage electrical stimulation (CVES), when applied within the same beef carcass (n = 79), on longissimus thoracis et lumborum (LTL) quality and palatability. There was a stimulation method × time interaction for pH, with CCES reducing the 3 h post-mortem pH, but increasing the 72 h post-mortem pH compared to CVES (P < 0.001). The CCES decreased the meat subjective Japanese Meat Grading Agency (JMGA) colour scores (P < 0.05) and increased the objective L⁎ (P < 0.01), a⁎ (P < 0.05) and b⁎ (P < 0.05) colour values at 3 d post-mortem and L⁎ and b⁎ values (P < 0.05) during retail display compared to CVES, although the objective values from both stimulation methods were above established consumer acceptability thresholds. Additionally, CCES reduced the purge (P < 0.05) and drip (P < 0.01) losses, and tended to reduce shear force values (P = 0.089) compared to CVES, although these did not translate into differences in juiciness or tenderness evaluated by trained panelists (P > 0.1). Regarding flavour, the CCES meat had greater bloody/serumy flavour (P < 0.05) and corn aroma (P < 0.05), less unidentified aroma (P < 0.05), and tended to have greater corn flavour (P = 0.077) and less barnyard aroma (P = 0.079) than CVES meat. There were also increased concentrations of flavour-related volatile compounds including 2-methyl-butanal, 3-methyl-butanal and 2–5-dimethyl pyrazine levels (P < 0.05) with CCES. Overall, the CCES system slightly improved meat quality and flavour compared to CVES when applied to the same beef carcasses. Further consumer studies would be warranted to determine whether these differences translate into more acceptable meat.

Contrast-Enhanced Ultrasound (CEUS) Evaluation of Canine Prostatic Hyperplasia before and after Osaterone Acetate Therapy: Preliminary Results.

The prostate is the only sexual gland of the male dog, and dihydrotestosterone (DHT) regulates its growth. In intact dogs, constant DHT stimulation results in benign prostatic hyperplasia (BPH) that can be treated with osaterone acetate (OSA). This study describes the effects of OSA treatment, detected by contrast-enhanced ultrasonography (CEUS), highlighting prostatic vascularization with a contrast agent composed of gas microbubbles. Fifteen dogs (2-8 years) of different sizes and breeds (4-30 kg) diagnosed with BPH are involved in the study. Before treatment (D0), CPSE is measured (294.05 ± 115.97 ng/mL), and a B-mode ultrasound is performed (Vratio = 2.80 ± 1.85), confirming BPH. CEUS highlights the length of the wash-in (11.93 ± 2.08 s) and wash-out (42.20 ± 6.99 s) phases of the contrast agent in the prostate and the presence of cysts and parenchymal alteration. Dogs are treated with OSA (0.5 mg/kg for 7 days) and reassessed after 21 days (D1): CPSE and prostate volume are significantly (p < 0.001) reduced. The length of the wash-in (14.73 ± 2.54 s) and wash-out (51.13 ± 6.03 s) phases are significantly (p < 0.001) increased. The results confirm the effectiveness of the treatment, particularly the reduction in prostatic perfusion, confirmed by the increase in diffusion times of the contrast. Although preliminary, these findings are promising for the use of CEUS in monitoring dogs with BPH.

Design of CMOS Analog Front-End Local-Field Potential Chopper Amplifier With Stimulation Artifact Tolerance for Real-Time Closed-Loop Deep Brain Stimulation SoC Applications.

A CMOS analog front-end (AFE) local-field potential (LFP) chopper amplifier with stimulation artifact tolerance, improved right-leg driven (RLD) circuit, and improved auxiliary path is proposed. In the proposed CMOS AFE LFP chopper amplifier, common-mode artifact voltage (CMAV) and differential-mode artifact voltage (DMAV) removal using the analog template removal method are proposed to achieve good signal linearity during stimulation. An improved auxiliary path is employed to boost the input impedance and allow the negative stimulation artifact voltage passing through. The common-mode noise is suppressed by the improved RLD circuit. The chip is implemented in 0.18- μm CMOS technology and the total chip area is 5.46-mm2. With the improved auxiliary path, the measured input impedance is larger than 133 M[Formula: see text] in the signal bandwidth and reaches 8.2 G[Formula: see text] at DC. With the improved RLD circuit, the measured CMRR is 131 - 144 dB in the signal bandwidth. Under 60-μs pulse width and 130-Hz constant current stimulation (CCS) with ±1-V CMAV and ±50-mV DMAV, the measured THD at the SC Amp output of fabricated AFE LFP chopper amplifier is 1.28%. The measurement results of In vitro agar tests have shown that with ±1.6-mA CCS pulses injecting to agar, the measured THD is 1.69%. Experimental results of both electrical and agar tests have verified that the proposed AFE LFP chopper amplifier has good stimulation artifact tolerance. The proposed CMOS AFE LFP chopper amplifier with analog template removal method is suitable for real-time closed-loop deep drain stimulation (DBS) SoC applications.

Moving Waste Sector Towards Climate Neutrality. Scenario Analysis

The upward economic growth, the development of the industrial, transport and agricultural sectors, and technological innovations contribute to the constant stimulation of the demand and supply of new products and services, inevitably contributing to the increase in the amount of waste. Mitigation of climate change is not a short-term goal; therefore, sustainable and reasonable practices in the waste management sector could contribute to positive changes in mitigating GHG emissions and climate change in general. However, it is not clear whether by implementing the current domestic waste management policy of Latvia and the action measures contained in it, it is objectively possible to achieve the strategic goals and desired results set at the European Union as well as at the national level, what is the impact of the set goals and the success of their implementation so far, and whether these political settings will not remain only at the level of ideas and wishes. In the scientific literature, several proposals developed as a result of research have been put forward for reducing the climate neutrality of the waste sector with the help of various technologies and technological innovations. At the same time, it is difficult to evaluate the proposals and solutions put forward in the research results in relation to an individual situation; for example, if a municipality in Latvia would like to implement it in order to evaluate their effectiveness, benefits and applicability. Difficulties are caused by the research results presented in the scientific literature, which are not expressed as indicators that would help to apply this solution to each individual case and its characteristic values. The purpose of the study is to evaluate the political goals set by Latvia in the household waste management sector in the context of the political goals set by the European Union for achieving climate neutrality and to provide an objective assessment of the achievement of the goals set by Latvia. In order to achieve the goals, an analysis of the scenarios of the household waste management sector established by Latvia's policy will be carried out, an evaluation of the actions implemented as a result of the policy and still planned will be carried out. Also, in order to achieve the goals of the study, indicators will be developed, with the help of which the effectiveness and applicability of the implementation of various technological innovations could be assessed. The development of indicators will be based on the information reflected in the scientific literature about the results of the implementation of technological innovations in the household waste management sector. As a result of the literature analysis, the absolute values of the selection of criteria for the implementation of technological innovations will be determined, as well as key performance indicators will be determined in such categories as technological solution, economic factor, impact (mitigation) on the environment, social factor. The scientific novelty of the research is based on the creation of a value database of the criteria for the implementation of technological innovations, and the development of an evaluation matrix based on it, based on the collected indicators, which would help to assess the applicability and availability of the technological innovations introduced in the waste management sector in order to promote the goals set in the political documents for achieving climate neutrality. As a result of the research, an assessment of the compliance of the climate neutrality goals set in the political planning documents will be carried out based on the indicators included in the developed matrix, in order to achieve the best waste management solutions.

Optically stimulated luminescence properties of In-doped CsBr transparent ceramics

0.01, 0.1, 0.5, and 1% In-doped CsBr transparent ceramics were synthesized by the spark plasma sintering method. Their photoluminescence and optically stimulated luminescence (OSL) properties were evaluated. All the samples showed transparency with transmittances of 40–60%. Luminescence due to 3P1–1S0 transitions of In + appeared at 500 nm. OSL emission peaks were confirmed at 500 nm upon constant stimulation light at 630 nm. A 0.1% In-doped sample showed the highest OSL intensities in prepared samples and the dose-response relationship was linear from 0.01 to 1000 mGy. The spatial resolution of X-ray images was confirmed from 5.00 LP/mm by using OSL of a 0.1% In-doped sample.

Duyu Bütünleme Sistemleri ile Eğitim İlişkisinde Nörolojik Fonksiyonların İncelenmesi

The aim of this study is to investigate the neurological functions in the relationship between sensory integration systems and education. Sensory integration, first of all, Occupational Therapist A. It was described by Jean Ayres as expressing a neurological process that allows us to make sense of our world by taking, recording, modulating, organizing and interpreting information from our senses to our brain. Neuroplasticity, which is the main component of sensory integration, is defined as changes in the structural properties and functions of neurons and synapses provided by these neurons in the brain depending on environmental stimuli. It has been argued in various studies examining the relationship between learning and brain cells that new axon strands occur Decently in neurons as a result of the learning process. According to this, the formation of new synaptic connections is due to each learning experience. Excessive use of synaptic connections in the brain leads to a strengthening of these connections. If these connections are not used, they will die and disappear. The development process of the brain is in the form of the formation (release of knots) and pruning of synaptic connections Tue. For this reason, constant stimulation of the brain with enriched experiences for the brain is important in the development of the brain. In ancient times, people thought that when they got older, their brains became stable. In recent years, due to technological developments, it has been understood that the human brain adapts to innovations that do not stop. In other words, the concept of flexibility of nerves, which we call neuroplasticity, has emerged. Key Words: Sensory Integration, Education, Neurological Functions

Experimental study of the mechanical properties and microscopic mechanism of carbonate rock subjected to high-temperature acid stimulation

To clarify the effect of acidification on the stress distribution around wells in deep carbonate reservoirs, it is necessary to study the changes in mechanical properties of carbonate rocks under different acid stimulation conditions. In this paper, a novel acid stimulation experiment is designed to investigate the mechanical properties of the carbonate rock through a self-built acid-rock reaction experimental system and triaxial rock mechanics apparatus. The changes in the core mechanical parameters with the acid stimulation time at different acid stimulation temperatures are obtained. Based on stress relaxation, the rheological properties of the core after acid stimulation are explored. The internal structural damage mechanism of the core after high-temperature acid stimulation is as analysed via by SEM. This research finds that the elastic modulus and compressive strength of the core exponentially decrease with increasing of acid stimulation time. The higher the acid stimulation temperature, the faster the core damage rate changes, and the earlier the damage amount tends to stabilize. The core has an obvious rheological mechanical property after acid stimulation. The stress relaxation amplitude exponentially increases with increasing strain during loading. Interestingly, when the acid stimulation temperature reaches 120 °C, a sudden stress drop occurs during stress relaxation. It is also found that the stress relaxation amplitude increases exponentially with increasing acid stimulation time under the same strain level. Moreover, a higher acid stimulation temperature results in greater stress relaxation under a constant acid stimulation time and strain. In addition, the core skeleton is destroyed through acid stimulation, and many complex damaged structures appear inside the core, which leads to a decrease in the core strength, which is the reason for the enhanced rheological characteristics of the rock after acid stimulation. These results can provide insights into the mechanical response mechanism of wellbore acidification.

Abstract 6326: Targeting PRDM1 to enhance CAR T cell efficacy against diffuse large B cell lymphoma (DLBCL)

Abstract CAR T cell therapy has shown remarkable success in treating patients with relapsed or refractory (r/r) DLBCL, but a majority (&amp;gt;60%) will experience disease progression. A key failure mechanism is the rapid terminal differentiation and exhaustion of CAR T cells, driven by persistent antigen exposure in vitro during manufacturing and in vivo in the DLBCL environment, which culminates in poor persistence and short-term effector functions. Recent studies have identified the transcriptional repressor PR/SET domain 1 (PRDM1) as a key regulator that drives differentiation of T cells toward these unwanted fates. Further, single cell transcriptomic profiling of r/r DLBCL biopsies has revealed PRDM1 enrichment in a cluster of exhausted-like CD8+ CAR T cells. These observations indicate that targeting PRDM1 could prevent or delay terminal differentiation/exhaustion in CAR T cells, thereby enhancing their persistence for lasting anti-tumor activity. Using CRISPR/Cas9 targeting, we have demonstrated that PRDM1-deficient CAR T cells exhibit enhanced proliferative capacity, memory characteristics, and resilience against exhaustion upon repeated stimulation. Moreover, genetic ablation of PRDM1 also promoted the in vivo expansion and persistence of CAR T cells, which led to significantly improved survival of lymphoma-bearing mice. Mechanistically, loss of PRDM1 leads to de-repression of PPARGC1A (PGC1α), a master regulator of mitochondrial biogenesis and antioxidant activity. This confers elevated tolerance to oxidative damage in CAR T cells lacking PRDM1, which showed increased capacity to buffer oxidative stress induced by mitochondrial uncouplers and constant stimulation. These findings suggest that PRDM1 loss may improve CAR T cell fitness through PGC1α upregulation and mitochondrial activation. From a translational perspective, we assessed the potential synergistic effects of PGC1α agonist, bezafibrate, with CAR T cells. Dual therapy with bezafibrate and CAR T cells mediated more robust expansion and anti-tumor immunity of CAR T cells without causing discernible adverse events. Importantly, bezafibrate alone had no direct tumoricidal effects, which indicates that bezafibrate suppressed tumor growth through modulating CAR T cell functions. Moving forward, we will uncover the previously uncharted role of PRDM1 in orchestrating the mitochondrial and metabolic activity of CAR T cells. Building upon a correlation between PRDM1 expression and CAR T cell dysfunction, we aim to pioneer the use of PRDM1 and/or its target genes as novel biomarkers for predicting clinical responses of r/r DLBCL patients to CAR T cell therapy. Our endeavors will shed light on the long-standing conundrum of CAR T cell dysfunction and offer solutions that may be applicable for improving T cell-based therapy against cancer in general. Citation Format: Sidney Wang, Lishi Xie, Xiufen Chen, Alan Cooper, Joanna Chorazeczewski, Justin Kline. Targeting PRDM1 to enhance CAR T cell efficacy against diffuse large B cell lymphoma (DLBCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6326.

Nonwoven Reinforced Photocurable Poly(glycerol sebacate)-Based Hydrogels.

Implantable hydrogels should ideally possess mechanical properties matched to the surrounding tissues to enable adequate mechanical function while regeneration occurs. This can be challenging, especially when degradable systems with a high water content and hydrolysable chemical bonds are required in anatomical sites under constant mechanical stimulation, e.g., a foot ulcer cavity. In these circumstances, the design of hydrogel composites is a promising strategy for providing controlled structural features and macroscopic properties over time. To explore this strategy, the synthesis of a new photocurable elastomeric polymer, poly(glycerol-co-sebacic acid-co-lactic acid-co-polyethylene glycol) acrylate (PGSLPA), is investigated, along with its processing into UV-cured hydrogels, electrospun nonwovens and fibre-reinforced variants, without the need for a high temperature curing step or the use of hazardous solvents. The mechanical properties of bioresorbable PGSLPA hydrogels were studied with and without electrospun nonwoven reinforcement and with varied layered configurations, aiming to determine the effects of the microstructure on the bulk compressive strength and elasticity. The nonwoven reinforced PGSLPA hydrogels exhibited a 60% increase in compressive strength and an 80% increase in elastic moduli compared to the fibre-free PGSLPA samples. The mechanical properties of the fibre-reinforced hydrogels could also be modulated by altering the layering arrangement of the nonwoven and hydrogel phase. The nanofibre-reinforced PGSLPA hydrogels also exhibited good elastic recovery, as evidenced by the hysteresis in compression fatigue stress-strain evaluations showing a return to the original dimensions.

The role of lateral hypothalamic nucleus in mediating locomotive behaviors in pigeons (Columba livia)

The lateral hypothalamic nucleus (LHy) is located in the dorsolateral hypothalamus of birds, and it is essential to many life processes. However, limited information is available about the role of LHy in mediating locomotive behaviors. In this work, we investigated the structure and function of LHy in pigeons (Columba livia) by Nissl staining, immunohistochemical (IHC) staining, insituhybridization (ISH) staining and constant current stimulation methods. The results showed that LHy appears crescent in shape, and three-dimensional coordinate value range of LHy is: A: 5.0–8.0 mm, L: 0.7–1.2 mm, D: 9.5–10.3 mm. The dopaminergic neurons in LHy were distributed in small amount and concentrated manner, while the glutamatergic neurons were distributed in a large number and uniform manner. The distribution of the above two neurons at each coronal level showed a significant positive correlation (R2 = 0.7516, P < 0.001). Our work demonstrated that LHy mainly mediates forward movement (P < 0.01) and ipsilateral lateral movement (P < 0.001), and these movements were significantly effected by electrical stimulation intensity. Our results showed that LHy can mediate the generation of directional behavior and this will provide technical support for the study of locomotor behavior regulation in birds.

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

STRESS-INDUCED HYPERTHERMIA (LITERATURE REVIEW)

Stress-induced hyperthermia (SIH) is a physiological response of the body to psychological stress. Currently, 88 % of the population is in a state of chronic stress. Psychogenic hyperthermia is more common in young women. Psychogenic fever is not associated with an immunological inflammatory process, there is no increase in inflammatory mediators. The mechanism of the development of stress-induced hyperthermia is the activation of the sympathoadrenal system, vasoconstriction, an increase in the level of corticosterone and the thermogenesis of brown fat. Constant sympathetic stimulation leads to the formation of thermogenin-expressing loci in white adipose tissue. Dopaminergic and noradrenergic compounds do not affect the intensity of hyperthermia. Taking nonsteroidal analgesics does not affect this type of hyperthermia. Antipsychotics are ineffective for psychogenic hyperthermia. Effective drugs that have anxiolytic properties, which significantly reduce the basal body temperature when the dose is increased. Serotonergic receptors play a key role in modulating behavioural, autonomic, and endocrine responses to stress. Effective GABA agonists and antidepressants. For the treatment of the chronic variant of SIH, the use of fluoxetine is recommended. Psychoeducation is used as non-medicinal methods of treating functional fever; psychotherapy with an adjustment environment (verbal or non-verbal release of unreacted negative emotions and conflicts); cognitive-behavioral or other psychological therapy, meditation, relaxation training; yoga and practices aimed at reducing stress and mental disorders.

The safety and feasibility of transcranial direct current stimulation for patients with chronic severe traumatic brain injury in Japan, a phase I study

BackgroundDespite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury. MethodsWe verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability). ResultsSix patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point. ConclusionOur phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).