Search Results (179)

Background/Objectives: Recent studies have investigated the effects of ketamine on fear memory in animals. However, it is unclear if ketamine might affect avoidance memory and emotional behaviors concomitantly. In this study, we compared the effects of (R,S)- and (S)-ketamine in modulating avoidance responses, depression- and anxiety-related behaviors in stressed mice. Methods: Mice were previously exposed to inescapable footshock stress, and 24 h later, they were trained in the active avoidance task. (R,S)-ketamine or (S)-isomer was administered 1 h prior to re-exposition to the active avoidance task. Three hours after drug administration, mice were tested in the tail suspension, followed by the open field test. Results: Neither form of ketamine affected avoidance memory retrieval, while (S)-ketamine, and tangentially, (R,S) reduced avoidance responses during re-exposition to aversive stimulus. In the tail suspension test, (R,S)- and (S)-ketamine equally evoked antidepressant effects. In the open field test, the racemic mixture, but not (S)-ketamine, induced anxiolytic actions. Conclusions: These findings reinforce the therapeutic potential of ketamine for the treatment of stress-related disorders, with (R,S)-ketamine being more effective in simultaneously inducing antidepressant and anxiolytic responses and reducing avoidance responses in stressed mice. Full article

This study examines the in-situ lateral static load behavior of a closed-diaphragm wall foundation, aiming to better understand its load–displacement response, structural behavior, and soil interaction under horizontal loading. An in-situ static load test was conducted with a maximum applied load of 70 MN, revealing that the diaphragm wall initially exhibits a linear load–displacement response, which becomes increasingly nonlinear as the load increases. The horizontal displacement of the lateral walls is nearly identical to the overall displacement of the diaphragm wall, making it a reliable indicator of the wall’s load state, particularly when it is challenging to measure total displacement. The wall behaves as a rigid body with minimal relative displacement between sections, and overturning failure is identified as the primary failure mode. Earth pressure distribution varies around the wall: passive earth pressure is observed at the front edge, while active and passive pressures alternate at the rear edge. These findings provide valuable insights into the design of diaphragm wall foundations, emphasizing the importance of lateral displacements. Full article

Demands for increasing the velocity and load carrying capacity of railway vehicles are a challenge to the passive suspension systems used for isolating the lateral vibrations of the carbody of a railway vehicle, especially under a wide range of vibration frequencies. Semiactive suspension systems, especially systems with a magnetorheological damper (MRD), have been investigated as promising alternatives. Many control algorithms have been developed for fine-tuning the damping force generated by MRDs, but they have been ineffective in isolating carbody vibrations at or around the resonance frequencies of the carbody and bogie. This study aims to develop a mixed control algorithm for a new skyhook (SH) control and a new displacement–velocity (DV) control to improve the effectiveness of vibration isolation in resonance frequency regions while producing high performance across the remaining frequencies. The damping coefficient of the new SH controller depends on the vibration velocity of the components of the suspension system and the skyhook damping variable, whereas that of the new DV controller depends on the velocity and displacement of the components of the suspension system and the stiffness variable. The values of the skyhook damping variable and stiffness variable were identified from the vibration velocity of the carbody using the trial and error method. The results of a numerical simulation problem indicated that the proposed control method worked effectively at low frequencies, similar to the conventional SH–DV controller, whereas it significantly improved ride comfort at high frequencies; at the resonance frequency of the bogie (14.6 Hz), in particular, it reduced the vibration velocity and acceleration of the carbody by 50.85% and 45.39%, respectively, compared with the conventional mixed SH–DV controller. The simplicity and high performance of the new mixed SH–DV control algorithm makes it a promising tool to be applied to the semiactive suspension of railway vehicles in real-world applications. Full article

Tobacco BY-2 cell culture is one of the most widely used models in plant biology. The main advantage of BY-2 suspension cultures is the synchronization of cell development and the appearance of polar elongation. In batch culture, BY-2 cells passed through the lag, proliferation, elongation, and stationary phases. During this process, the composition of the growth medium changed dramatically. Sucrose was rapidly eliminated; hexose first accumulated and then depleted. The medium’s pH initially decreased and then rose with aging. As a result of the crosstalk between the internal and external stimuli, cells pass through complicated systemic rearrangements, which cause metabolomic alterations. The early stages were characterized by high levels of amino acids and sterols, which could be interpreted as the result of synthetic activity. The most intense rearrangements occurred between the proliferation and active elongation stages, including repression of amino acid accumulation and up-regulation of sugar metabolism. Later stages were distinguished by higher levels of secondary metabolites, which may be a non-specific response to deteriorating conditions. Senescence was followed by some increase in fatty acids and sterols as well as amino acids, and probably led to self-destructive processes. A correlation analysis revealed relationships between metabolites’ covariation, their biochemical ratio, and the growth phase. Full article

The articulated single-axle straddle-type monorail train has many unique advantages, making it the preferred choice for medium-capacity urban rail transit. However, the issue of vehicle shimmy greatly restricts its promotion and application. In response to this issue, an active suspension control scheme is proposed, and the corresponding control algorithm is designed. Considering economic and feasible factors, a modification plan for the single-axle bogie without changing the original structure is proposed. A closed-loop feedback control strategy with lateral velocity and yaw rate as control objectives is designed, and a 114 degree-of-freedom dynamic model of a monorail train is established. Taking the skyhook damping control as the reference model, the SH-SMC (skyhook-sliding mode control) active control scheme is designed based on the sliding mode control theory. Considering practical applications, the control force distribution algorithm is further proposed. Through co-simulation of UM and Matlab, different control schemes are compared and analyzed. The results indicate that the SH-SMC active control scheme is more effective in suppressing the shimmy of single-axle monorail train, verifying the effectiveness of the SH-SMC active control scheme. It is of great significance for the further promotion and application of single-axle monorail trains in more cities. Full article

This study examines the three-axis vibration isolation capabilities of a full-scale magnetorheological (MR) seat suspension system utilizing experimental methods to assess performance under both single-axis and simultaneous three-axis input conditions. To achieve this, a semi-active MR seat damper was designed and manufactured to address excitations in all three axes. The damper effectiveness was tested experimentally for axial and lateral motions, focusing on dynamic stiffness and loss factor using an MTS machine. Prior to creating the full-scale MR seat suspension, a scaled-down version at one-third size was developed to verify the damper’s ability to effectively reduce vibrations in response to practical excitation levels. Additionally, a narrow-band frequency-shaped semi-active control (NFSSC) algorithm was developed to optimize vibration suppression. Ultimately, a full-scale MR seat suspension was assembled and tested with a 50th percentile male dummy, and comprehensive three-axis vibration isolation tests were conducted on a hydraulic multi-axis simulation table (MAST) for both individual inputs over a frequency range up to 200 Hz and for simultaneous multi-directional inputs. The experimental results demonstrated the effectiveness of the full-scale MR seat suspension in reducing seat vibrations. Full article

Depression is a complex psychiatric disorder that has substantial implications for public health. The lateral habenula (LHb), a vital brain structure involved in mood regulation, and the N-methyl-D-aspartate receptor (NMDAR) within this structure are known to be associated with depressive behaviors. Recent research has identified transcription factor 7-like 2 (TCF7L2) as a crucial transcription factor in the Wnt signaling pathway, influencing diverse neuropsychiatric processes. In this study, we explore the role of TCF7L2 in the LHb and its effect on depressive-like behaviors in mice. By using behavioral tests, AAV-mediated gene knockdown or overexpression, and pharmacological interventions, we investigated the effects of alterations in TCF7L2 expression in the LHb. Our results indicate that TCF7L2 expression is reduced in neurons within the LHb of male ICR mice exposed to chronic mild stress (CMS), and neuron-specific knockdown of TCF7L2 in LHb neurons leads to notable antidepressant activity, as evidenced by reduced immobility time in the tail suspension test (TST) and forced swimming test (FST). Conversely, the overexpression of TCF7L2 in LHb neurons induces depressive behaviors. Furthermore, the administration of the NMDAR agonist NMDA reversed the antidepressant activity of TCF7L2 knockdown, and the NMDAR antagonist memantine alleviated the depressive behaviors induced by TCF7L2 overexpression, indicating the involvement of NMDAR. These findings offer novel insights into the molecular mechanisms of depression, highlighting the potential of TCF7L2 as both a biomarker and a therapeutic target for depression. Exploring the relationship between TCF7L2 signaling and LHb function may lead to innovative therapeutic approaches for alleviating depressive symptoms. Full article

One of the most common reasons a patient would see an otolaryngologist is for nasal obstruction. This article provides an overview of the physical principles related to nasal airflow as well as the critical role that the internal nasal valve plays in regulating airflow resistance. Common treatment options for internal nasal valve obstruction are discussed as well as an in-depth tutorial on an alternate lateral nasal suspension suture technique for internal nasal valve collapse. Full article

The mesolimbic reward system originating from dopamine neurons in the ventral tegmental area (VTA) of the midbrain shows a profound reduction in function during cannabinoid withdrawal. This condition may underlie aversive states that lead to compulsive drug seeking and relapse. The lateral habenula (LHb) exerts negative control over the VTA via the GABA rostromedial tegmental nucleus (RMTg), representing a potential convergence point for drug-induced opponent processes. We hypothesized that the LHb–RMTg pathway might be causally involved in the hypodopaminergic state during cannabinoid withdrawal. To induce Δ⁹-tetrahydrocannabinol (THC) dependence, adult male Sprague–Dawley rats were treated with THC (15 mg/kg, i.p.) twice daily for 6.5–7 days. Administration of the cannabinoid antagonist rimonabant (5 mg/kg, i.p.) precipitated a robust behavioral withdrawal syndrome, while abrupt THC suspension caused milder signs of abstinence. Extracellular single unit recordings confirmed a marked decrease in the discharge frequency and burst firing of VTA dopamine neurons during THC withdrawal. The duration of RMTg-evoked inhibition was longer in THC withdrawn rats. Additionally, the spontaneous activity of RMTg neurons and of LHb neurons was strongly depressed during cannabinoid withdrawal. These findings support the hypothesis that functional changes in the habenulo–mesencephalic circuit are implicated in the mechanisms underlying substance use disorders. Full article

There is an urgent need to alleviate the symptoms of neurodegenerative diseases. The presented work includes the use of electrochemical polymerization (CV) to obtain active polypyrrole layers with incorporated molecules of a neurological drug substance—amantadine hydrochloride. The obtained films were characterized chemically, structurally, and functionally in terms of their use as a drug delivery systems which are neurologically active. FTIR spectra were recorded to identify the incorporation of drug substances into the matrix. The obtained results showed that amantadine and heparin were embedded to the polypyrrole matrix. Scanning electron microscopy (SEM) was used to examine the morphology of the films. The films deposited on the steel substrate showed a compact, smooth structure, where there was no visible organized structure. After release, the film became corrugated. Adhesive tests were conducted with the cross-cut Test Method B to determine the mechanical properties, and the results showed that amantadine improves adhesion for steel substrates. The films were potentially stimulated by chronoamperometry, and UV-Vis spectra were registered to calculate the concentration of AMA in the solution after release. The release curves indicate a 95% efficiency of AMA release over the studied time period and protocol. Later, antibacterial properties were tested. The proposed system was able to provide a daily dose of drugs that ensures a therapeutic effect. This is a significant step towards developing systems capable of delivering a wider range of doses, potentially in line with the full spectrum recommended for therapeutic efficacy. The antibacterial properties of the material allows it to be considered as a material with antibacterial potential in the presence of the Staphylococcus aureus (S. aureus) strain. The percentage reduction ratio indicates a 90–100% reduction of bacteria in the suspension. Full article

In grassland agroecosystems, some plant pathogenic bacteria can cause disease in animals. These strains are known as plant and animal cross-kingdom pathogenic bacteria. In this study, we established an alfalfa root infection model and a mouse model via the gavage administration of the Pantoea alfalfae CQ10 (CQ10) bacterial suspension. It was confirmed that the CQ10 strain caused bacterial leaf blight of alfalfa. Mice inoculated with 0.4 mL of 10⁹ cfu/mL bacterial suspension developed clinical symptoms 48 h later, such as diminished vitality, tendencies to huddle, and lack of appetite, including severe lesions in stomach, liver, kidney, and spleen tissues. CQ10 strains were isolated from mouse feces at different time points of inoculation. Thus, CQ10 is a plant and animal cross-kingdom pathogenic bacterium. Transcriptome and proteome analyses showed that biofilm and iron uptake are important virulence factors of the pathogen CQ10, among which Bap and Lpp regulating biofilm are the key cross-kingdom virulence genes of CQ10. From an evolutionary perspective, insights gained from this dual animal–plant pathogen system may help to elucidate the molecular basis underlying the host specificity of bacterial pathogens. The result provides a theoretical basis for the risk assessment, prevention, and control strategies of new pathogenic bacteria entering a new region. Full article

Whether SARS-CoV-2 infection leads to a higher mortality and morbidity in people living with HIV (PLWH) in Africa remains inconclusive. In this study, we explored the differences in the T-cell phenotypes between people with and without HIV on the day of admission (V1) and ±7 days later (V2), as well as their cytokine/chemokine profiles on V1. Patients admitted with COVID-19 were recruited between May 2020 and December 2021 from the Steve Biko Academic and Tshwane District Hospitals in Pretoria, South Africa. Of 174 patients, 37 (21%) were PLWH. T-cell profiles were determined by flow cytometry, and cytokine levels were determined using a multiplex suspension bead array. PLWH were significantly younger than those without HIV, and were more likely to be female. In an adjusted analysis, PLWH had higher percentages of CD4+ central memory (CM) programmed cell death protein 1 (PD-1)+, CD8+ effector memory (EM)2, and CD8+ EM4 CD57+ cells, as well as higher concentrations of interleukin (IL)-35 at admission. PLWH with CD4+ T-cell counts of >200 cells/mm³ had altered CD4+ and CD8+ T-cell profiles, lower levels of systemic inflammation measured by plasma ferritin and PCT levels, and less severe disease. PLWH with CD4+ T-cell counts of <200 cells/mm³ on admission had higher concentrations of IL-6 and lower levels of IL-29. At V2, the percentages of CD4+ CM PD-1+ T-cells and CD8+ EM4 T-cells co-expressing CD57 and PD-1 remained higher in PLWH, while all other CD8+ EM populations were lower. Fewer CD8+ EM T-cells after ±7 days of admission may be indicative of mechanisms inhibiting EM T-cell survival, as indicated by the higher expression of IL-35 and the T-cell maturation arrest observed in PLWH. This profile was not observed in PLWH with severe immunodeficiency, highlighting the need for differentiated care in the broader PLWH population. Full article

Background: Minimally invasive surgery could improve cosmetic outcomes and reduce the risks of surgical injury with less postoperative pain and a quicker patient’s discharge. Recently, transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has been introduced in urogynecology with exciting results. Evidence Acquisition: After PROSPERO registration (n°CRD42023406815), we performed a comprehensive literature search on Pubmed, Embase, and Cochrane CENTRAL, including peer-reviewed studies evaluating transvaginal natural orifice transluminal endoscopic surgery. No limits on time or type of study were applied. Evidence synthesis: Overall, 12 manuscripts were included in the analysis. Seven studies evaluated uterosacral ligament suspension, four studies evaluated sacral colpopexy, three evaluated sacrospinous ligament suspension, and one study evaluated lateral suspension. Overall success rates were high (>90%); however, definitions of success were heterogeneous. In terms of complication, most of the studies reported low-grade complications (Clavien–Dindo I and II); only two patients needed mesh removal because of mesh exposure. The risk of bias of the trials was rated in the medium to high-risk category. Conclusions: The present review highlights important initial results for vNOTES. Future randomized clinical trials are needed to better define its role in the management of urogynecological procedures. Full article

We have previously observed that mice exposed to social defeat stress are more sensitive to cocaine in the conditioned place preference (CPP) paradigm. In this context, it has been suggested that the nitric oxide (NO) pathway plays a role in the effects of stress. The present study evaluates the role of a neuronal NO synthase (nNOS) inhibitor (7-nitroindazole, 7-NI) in the short- and long-term behavioural effects of intermittent social defeat (ISD). Four groups of mice were employed for the study: a control group and three stressed groups, one treated with vehicle and two treated with 7-NI (7.25 or 12.5 mg/kg). After the last episode of defeat, mice were tested in the elevated plus maze (EPM), social interaction, object recognition and tail suspension tests. Three weeks later, mice were conditioned with cocaine (1 mg/kg). Stressed mice, irrespective of the treatment received, showed anxiety in the EPM, presented a deficit of social interaction and spent less time immobile in the tail suspension test. However, only stressed mice treated with vehicle developed CPP. Thus, although 7-NI did not modify the short-term behavioural effects of ISD, it prevented ISD-induced potentiation of the rewarding properties of cocaine in adulthood. These results support a specific role of nNOS in the effects of social stress on drug reward. Full article

Owing to medical historian Erwin H. Ackerknecht’s (1906–1988) pioneering study “Medicine at the Paris Hospital, 1794–1848” (1967), the year 1794 is seen as the decisive separation date on which the development and reorganization of the Parisian clinical school—as a broad movement and a system of medical education and clinical practice—distanced it from the traditions of the 18th century. This precise dating is based on the “Rapport et projet de décret sur l’établissement d’une École centrale de Santé à Paris” (1794) by the French clinician and naturalist Antoine-François Fourcroy (1755–1809), which appeared five years after the French Revolution. Fourcroy was asked by the Conseil d’État to submit a detailed report in which he was obliged to comment on the existing health situation and the state of medical care and research. His report thereby ventured so far as to request the continued dissolution of all medical faculties in France, as these institutions were seen as counter-revolutionary hotbeds in the wider educational landscape of the Grande Nation. Fourcroy’s recommendations were implemented a short time later; he had recommended that medical training should be established again in the traditional locations of Paris, Montpellier, and Strasbourg in France yet in the different settings of so-called health schools, Écoles de Santé. In this article, I look at the corresponding training and care structures after the French Revolution, as well as some of the specific reasons which led to the complete suspension of teaching in academic medicine at the time. In the more recent research literature, Ackerknecht’s view has undergone some modifications, whereby the fixation on the date 1794 has been challenged since the French traditions of the royalistic period have hardly been considered. Furthermore, it has been argued that the reorganization of medicine during the time of the Empire remained largely based on knowledge structures derived from the previous 18th century. In order to keep the complex scientific, institutional, and socio-economic conditions of the context of Parisian Academic Medicine aligned, I first explore some developments up to the time of the French Revolution (1789), before assessing the implications of the reform of knowledge structures and curricular programs instigated since the 1790s, as these remain relevant to medical history in the 19th century. Full article