Secondary Response Research Articles

Effect of repeated seizures on spatial exploration and immediate early gene expression in the hippocampus and dentate gyrus

Immediate early genes (IEGs) are coordinately activated in response to neuronal activity and can cause activation of secondary response genes that modulate synaptic plasticity and mediate long-lasting changes in behaviour. Excessive neuronal stimulation induced by epileptic seizures induce rapid and dramatic changes in IEG expression. Although the impact of acute seizure activity on IEG expression has been well studied, less is known about the long-term effects of chronic seizures on IEG induction during seizure free periods where behavioural and cognitive impairments are frequently observed in people with epilepsy and in animal models of epilepsy. The present study sought out to examine the impact of chronic pentylenetetrazole evoked seizures (PTZ kindling) on spatial exploration induced in IEG expression (c-Fos, ΔFosB, Homer1a, Egr1, Npas4, Nr4a1) in the hippocampus (CA1 and CA3 subfields) and dentate gyrus of rats. Male rats underwent two weeks of PTZ kindling (every 2 days) or received vehicle injections and were placed into a novel open field arena for 30 min either 24 hrs or 4 weeks after the last treatment. Although exploratory activity was similar between PTZ kindled and vehicle controls when examined 24 hrs after the last treatment, we observed a significant reduction in spatial exploration induced expression of c-Fos, Egr1, and ΔFosB in the hippocampus and dentate gyrus, and reduced expression of Nr4a1 in the dentate gyrus and Homer1a in the hippocampus only. When testing was conducted after a 4-week recovery period, only c-Fos continued to show reduced expression after exposure a novel environment in previously PTZ kindled animals. Interestingly, these animals also showed reduced activity in the center region of the open field suggestive of heightened anxiety-like behaviour. Collectively, these results suggest that repeated seizures may lead to longterm downregulation in hippocampal IEG expression that can extend into seizure free periods thereby providing a critical mechanism for the development of cognitive and behavioural deficits that arise during chronic epilepsy

Primary Versus Secondary Gravity Wave Responses at F‐Region Heights Generated by a Convective Source

AbstractA 2D nonlinear, compressible model is used to simulate the acoustic‐gravity wave (AGW, i.e., encompassing the spectrum of acoustic and gravity waves) response to a thunderstorm squall‐line type source. We investigate the primary and secondary neutral AGW response in the thermosphere, consistent with waves that can couple to the F‐region ionospheric plasma, and manifest as Traveling Ionospheric Disturbances (TIDs). We find that primary waves at z = 240 km altitude have wavelengths and phase speeds in the range 170–270 km, and 180–320 m/s, respectively. The secondary waves generated have wavelengths ranging from ∼100 to 600 km, and phase speeds from 300 to 630 m/s. While there is overlap in the wave spectra, we find that the secondary waves (i.e., those that have been nonlinearly transformed or generated secondarily/subsequently from the primary wave) generally have faster phases than the primary waves. We also assess the notion that waves with fast phase speeds (that exceed proposed theoretical upper limits on passing from the mesosphere to thermosphere) observed at F‐region heights must be secondary waves, for example, those generated in situ by wave breaking in the lower thermosphere, rather than directly propagating primary waves from their sources. We find that primary waves with phase speeds greater than this proposed upper limit can tunnel through a deep portion of the lower/middle atmosphere and emerge as propagating waves in the thermosphere. Therefore, comparing a TID's/GWs phase speed with this upper limit is not a robust method of identifying whether an observed TID originates from a primary versus secondary AGW.

Measles and rubella in the North-West of Russia in period of elimination

Aim: To evaluate the epidemic situation on measles and rubella and to carry out the laboratory diagnostics of these infections in the North-West of Russia in the period of elimination.Materials and Methods. In 2016-2019 a total of 534 blood serum samples from patients with measles diagnosis, 210 – from patients with rubella diagnosis and 1251 – from patients with exanthema were studied by ELISA using “VectoMeasles-IgM” and “EIA-Rubella-IgM” test-systems.Results. Measles incidence in NWR varied from 0 to 0.96 per 100,000 in 2016 and 2019, respectively. Among measles patients the proportion of children and adults changed in 2018-2019, adults constituted 65.9%. Patients not vaccinated against measles and those with the unknown vaccination status were mainly involved in epidemic process (85%). High level of patients with revaccination status was revealed in 2018 (18.4%). These patients demonstrated high levels of IgG (>3.0 IU/ml) as well as high percentage of IgG avidity (>94.3%) on 4-7th day of rash onset thus evidencing secondary immune response. Molecular studies of the samples from patients revealed the circulation of D8 and B3 genotypes of measles virus. Strains of D8 and B3 genotypes were represented by 3 and 4 variants, respectively. Rubella incidence did not exceed 0.13 per 100,000. Strains of rubella virus of genotype 1E were detected.Conclusion. The data of annual measles incidence and molecular studies of circulating wild type measles viruses prove the on-going measles elimination process in the NorthWest of Russia. For rubella, the persistent phase of elimination was demonstrated in the region.

Non-additive gene interactions underpin molecular and phenotypic responses in honey bee larvae exposed to imidacloprid and thymol

Understanding the cumulative risk of chemical mixtures at environmentally realistic concentrations is a key challenge in honey bee ecotoxicology. Ecotoxicogenomics, including transcriptomics, measures responses in individual organisms at the molecular level which can provide insights into the mechanisms underlying phenotypic responses induced by one or more stressors and link impacts on individuals to populations. Here, fifth instar honey bee larvae were sampled from a previously reported field experiment exploring the phenotypic impacts of environmentally realistic chronic exposures of the pesticide imidacloprid (5 μg.kg−1 for six weeks) and the acaricide thymol (250 g.kg−1 applied via Apiguard gel in-hive for four weeks), both separately and in combination. RNA-seq was used to discover individual and interactive chemical effects on larval gene expression and to uncover molecular mechanisms linked to reported adult and colony phenotypes. The separate and combined treatments had distinct gene expression profiles which represented differentially affected signaling and metabolic pathways. The molecular signature of the mixture was characterised by additive interactions in canonical stress responses associated with oxidative stress and detoxification, and non-additive interactions in secondary responses including developmental, neurological, and immune pathways. Novel emergent impacts on eye development genes correlated with long-term defects in visual learning performance as adults. This is consistent with these chemicals working through independent modes of action that combine to impact common downstream pathways, and highlights the importance of establishing mechanistic links between molecular and phenotypic responses when predicting effects of chemical mixtures on ecologically relevant population outcomes.

A phase 3 study to assess the immunogenicity, safety, and tolerability of MenB-FHbp administered as a 2-dose schedule in adolescents and young adults

BackgroundThe MenB-FHbp vaccine is licensed to prevent meningococcal serogroup B disease on either a 2-dose (0, 6 months) or 3-dose (0, 1–2, 6 months) series. This phase 3 study further assessed the immunogenicity and safety of the 2-dose MenB-FHbp schedule. MethodsSubjects 10–25 years of age received MenB-FHbp (months 0, 6) and the quadrivalent meningococcal conjugate vaccine MenACWY-CRM (month 0). Primary immunogenicity endpoints included percentages of subjects achieving ≥ 4-fold increases from baseline in serum bactericidal antibody using human complement (hSBA) titers for 4 diverse, vaccine-heterologous primary serogroup B test strains and titers ≥ lower limit of quantitation (LLOQ; 1:8 or 1:16) for all 4 primary strains combined (composite response) after dose 2; a titer ≥ 1:4 is the accepted correlate of protection. Percentages of participants with hSBA titers ≥ LLOQ for 10 additional vaccine-heterologous strains were also assessed; positive predictive values of primary strain responses for secondary strain responses were determined. Safety was assessed. ResultsOverall, 1057 subjects received dose 1 and 946 received dose 2 of MenB-FHbp. Percentages of participants achieving ≥ 4-fold increases in hSBA titers against each primary strain after dose 2 ranged from 67.4% to 95.0% and the composite response was 74.3%. Primary strain responses were highly predictive of secondary strain responses. Most reactogenicity events were mild-to-moderate in severity and did not lead to withdrawal from the study. Adverse events (AEs) considered by the investigator to be related to vaccination occurred in 4.2% (44/1057) of subjects, and there were no serious AEs or newly diagnosed chronic medical conditions considered related to vaccination. ConclusionsMenB-FHbp administered at 0, 6 months was well tolerated and induced protective bactericidal antibody responses against diverse serogroup B strains. Findings provide further support for the continued use of MenB-FHbp on a 2-dose schedule in this population.

Inflammation in the Pathogenesis of Arrhythmogenic Cardiomyopathy: Secondary Event or Active Driver?

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiac disease characterized by arrhythmia and progressive fibro-fatty replacement of the myocardium, which leads to heart failure and sudden cardiac death. Inflammation contributes to disease progression, and it is characterized by inflammatory cell infiltrates in the damaged myocardium and inflammatory mediators in the blood of ACM patients. However, the molecular basis of inflammatory process in ACM remains under investigated and it is unclear whether inflammation is a primary event leading to arrhythmia and myocardial damage or it is a secondary response triggered by cardiomyocyte death. Here, we provide an overview of the proposed players and triggers involved in inflammation in ACM, focusing on those studied using in vivo and in vitro models. Deepening current knowledge of inflammation-related mechanisms in ACM could help identifying novel therapeutic perspectives, such as anti-inflammatory therapy.

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages.

Macrophages (MΦ) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MΦ. We found that infection of both subsets with RV resulted in a low TNF-α and a high interferon (IFN, type I and type III) release whereby M-MΦ produced far more IFNs than GM-MΦ. Thus, TNF-α production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MΦ compared to the addition of LPS to the uninfected cells the TNF-α response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-β one putative priming stimulus induced by RV. Small amounts of IFN-β were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MΦ to RV and LPS revealed an increased phosphorylation of NFκB (M-MΦ), but different to uninfected MΦ a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-β can prime MΦ to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MΦ defense to viral infection is modulated by a following exposure to a bacterial infection.

Adjuvant Activity of CpG-Oligonucleotide Administered Transcutaneously in Combination with Vaccination Using a Self-Dissolving Microneedle Patch in Mice.

In this study, we investigated the mechanism of transcutaneous adjuvant activity of the CpG-oligonucleotide (K3) in mice. Transcutaneous immunization (TCI) with an ovalbumin-loaded self-dissolving microneedle patch (OVA-sdMN) and K3-loaded hydrophilic gel patch (HG) increased OVA-specific Th2- and Th1-type IgG subclass antibody titers more rapidly and strongly than those after only OVA-sdMN administration. However, the antigen-specific proliferation of OVA-specific CD4+ T cells was similar between the OVA-only and the OVA+K3 groups. Population analysis of various immune cells in draining lymph nodes (dLNs) in the primary immune response revealed that the OVA+K3 combination doubled the number of dLN cells, with the most significant increase in B cells. Phenotypic analysis by flow cytometry revealed that B-cell activation and maturation were promoted in the OVA+K3 group, suggesting that direct B-cell activation by K3 largely contributed to the rapid increase in antigen-specific antibody titer in TCI. In the secondary immune response, a significant increase in effector T cells and effector memory T cells, and an increase in memory B cells were observed in the OVA+K3 group compared with that in the OVA-only group. Thus, K3, as a transcutaneous adjuvant, can promote the memory differentiation of T and B cells.

Epigenetic regulation of natural killer cell memory.

Immunological memory is the underlying mechanism by which the immune system remembers previous encounters with pathogens to produce an enhanced secondary response upon re-encounter. It stands as the hallmark feature of the adaptive immune system and the cornerstone of vaccine development. Classic recall responses are executed by conventional T and B cells, which undergo somatic recombination and modify their receptor repertoire to ensure recognition of a vast number of antigens. However, recent evidence has challenged the dogma that memory responses are restricted to the adaptive immune system, which has prompted a reevaluation of what delineates "immune memory." Natural killer (NK) cells of the innate immune system have been at the forefront of these pushed boundaries, and have proved to be more "adaptable" than previously thought. Like T cells, we now appreciate that their "natural" abilities actually require a myriad of signals for optimal responses. In this review, we discuss the many signals required for effector and memory NK cell responses and the epigenetic mechanisms that ultimately endow their enhanced features.

Persistent Childhood and Adolescent Anxiety and Risk for Psychosis: A Longitudinal Birth Cohort Study

BackgroundPersistent anxiety in childhood and adolescence could represent a novel treatment target for psychosis, potentially targeting activation of stress pathways and secondary nonresolving inflammatory response. Here, we examined the association between persistent anxiety through childhood and adolescence with individuals with psychotic experiences (PEs) or who met criteria for psychotic disorder (PD) at age 24 years. We also investigated whether C-reactive protein mediated any association. MethodsData from the Avon Longitudinal Study of Parents and Children (ALSPAC) were available in 8242 children at age 8 years, 7658 at age 10 years, 6906 at age 13 years, and 3889 at age 24 years. The Development and Well-Being Assessment was administered to capture child and adolescent anxiety. We created a composite score of generalized anxiety at ages 8, 10, and 13. PEs and PD were assessed at age 24, derived from the Psychosis-like Symptoms Interview. The mean of C-reactive protein at ages 9 and 15 years was used as a mediator. ResultsIndividuals with persistent high levels of anxiety were more likely to develop PEs (odds ratio 2.02, 95% CI 1.26–3.23, p = .003) and PD at age 24 (odds ratio 4.23, 95% CI 2.27–7.88, p < .001). The mean of C-reactive protein at ages 9 and 15 mediated the associations of persistent anxiety with PEs (bias-corrected estimate −0.001, p = .013) and PD (bias-corrected estimate 0.001, p = .003). ConclusionsPersistent high levels of anxiety through childhood and adolescence could be a risk factor for psychosis. Persistent anxiety is potentially related to subsequent psychosis via activation of stress hormones and nonresolving inflammation. These results contribute to the potential for preventive interventions in psychosis, with the novel target of early anxiety.

Mathematical modelling of tumour-immune interactions in presence of checkpoint inhibitor-based therapies for the treatment of cancer

Prolonged stimulation of CD8 T cells by tumour antigens lead to a state of exhaustion with simultaneous expression of checkpoints, namely, “programmed cell death protein 1 (PD-1)” and “cytotoxic T lymphocyte antigen 4 (CTLA4)” on their surfaces. Targeting the receptors with checkpoint inhibitor-based therapies can restore immune responses. The current work proposes a mathematical model for unravelling the effect of checkpoint inhibitors on tumour-immune interactions and subsequent tumour eradication. The proposed model predicts that in absence of checkpoint inhibitors, the primary immune response alone is sufficient to arrest the tumour growth only if the immune response is greater than the tumour growth rate. In presence of anti-PD1 monotherapy, the model prediction shows an increase in tumour mass with time followed by a decline and attainment of a steady value indicating that the anti-PD1 inhibitor is a key factor in regulating the primary immune response. Monotherapeutic regimen comprising anti-CTLA4 inhibitor is not as effective in arresting tumour growth as the anti-PD1 inhibitor as the effect of anti-CTLA4 is more pronounced on the secondary immune response. However, a combination therapeutic regimen of anti-PD1/anti-CTLA4 inhibitors was predicted to be more effective than the anti-PD1 monotherapy indicating a possible synergy between the anti-CTLA4 and anti-PD1 inhibitors. The results were validated with experimental observations.

The immunomodulatory effect of koumine on B cells under dependent and independent responses by T cells

Dysregulated activation of polyclonal B cells and production of pathogenic antibodies are involved in the development of rheumatoid arthritis (RA). Therefore, targeted B cell therapy is effective against RA. Gelsemium elegans (Gardn. & Champ.) Benth., a toxic plant widely distributed in Southeast Asia, has been used for treating rheumatoid pain, neuropathic pain, spasticity, skin ulcers, and cancers for many years in traditional Chinese medicine. Koumine, an alkaloid monomer from Gelsemium elegans Benth., exerts therapeutic effects against RA. However, whether koumine affects B cells remains unknown. In this study, the effect of koumine on B cells under T cell-independent (TI) and T cell-dependent (TD) immune responses is investigated in vitro and in vivo. Mouse primary B cells were obtained by immunomagnetic bead sorting, and immunomodulatory effects of koumine on the activation, proliferation, and differentiation of B cells were determined in TI and TD models induced by lipopolysaccharide (LPS) and anti-CD40 antibodies in vitro, respectively. The humoral immune responses of TI and TD were established using NP-AECM-FICOLL and NP-CGG in C57BL/6J mice, respectively. We found that koumine inhibited B cell differentiation in the TI model and inhibited B cell activation and proliferation in the TD model in vitro. Koumine also inhibited antibody secretion in TI immune response, TD initial immune response, and in TD secondary immune response. Our results reveal that koumine has a direct and indirect immune regulatory effect on B cells, showing that it can directly inhibit the differentiation and secretion of autoantibodies after abnormal activation of B cells, and indirectly inhibit the activation and proliferation of TD B cells to reduce the secretion of antibodies. It may be an important mechanism for its anti-RA effect in mice, providing a rationale and laboratory data support for the application of koumine in anti-human RA therapy.

A Hybrid Intelligent Model for Urban Seismic Risk Assessment from the Perspective of Possibility and Vulnerability Based on Particle Swarm Optimization

Assessing seismic risk is an essential element of urban risk management and urban spatial security work. In response to the issues posed by the complexity and openness of urban systems, the nonlinearity of driving factors, and sudden changes in geological processes that affect urban seismic research, this paper is based on a variety of intelligent algorithms to develop a hybrid intelligent model that integrates probability and vulnerability to evaluate and quantify the difference in the urban spatial units distribution of earthquake risk. We applied this model to Hefei, one of the few superlarge provincial capital cities on the “Tancheng-Lujiang” fault zone, one of the four major earthquake zones in China, which suffers frequent earthquakes. Our method combined the genetic algorithm (GA), particle swarm optimization (PSO), and backpropagation neural network methods (BP) to automatically calculate rules from inputted data on known seismic events and predict the probability of seismic events in unknown areas. Then, based on the analytic hierarchy process (AHP), spatial appraisal and valuation of environment and ecosystems method (SAVEE), and EMYCIN model, an urban seismic vulnerability was evaluated from the four perspectives of buildings, risk of secondary disasters, socioeconomic conditions, and urban emergency response capabilities. In the next step, the overall urban seismic risk was obtained by standardizing and superimposing seismic probability and vulnerability. Using the hybrid intelligent model, earthquake probability, seismic vulnerability, and overall seismic risk were obtained for Hefei, and the spatial characteristics of its overall seismic risk were examined. This study concludes that areas with very high, high, low, and very low earthquake risk in Hefei account for 8.10%, 31.90%, 40.94%, and 19.06% of its total area, respectively. Areas with very high earthquake risk are concentrated in the old city, the government affairs district, Science City, and Xinzhan District. This study concludes that government authorities of Hefei should target earthquake safety measures consisting of basic earthquake mitigation measures and pre- and postearthquake emergency measures. In the face of regional disasters such as earthquakes, coordinating and governing should be strengthened between cities and regions.

Factors Associated With Severity of Cubital Tunnel Syndrome at Presentation.

The outcomes of cubital tunnel syndrome surgery are affected by preoperative disease severity. The aim of this study was to identify factors associated with clinical and electrodiagnostic severity of cubital tunnel syndrome at presentation. We retrospectively identified 213 patients with electrodiagnostically confirmed cubital tunnel syndrome who underwent cubital tunnel surgery from July 2008 to June 2013. Our primary response variable was clinical cubital tunnel syndrome severity assessed by the McGowan grade. Our secondary response variables were sensory nerve action potential (SNAP) recordability, presence of fibrillations, and motor nerve conduction velocities (CVs) in the abductor digiti minimi (ADM) and first dorsal interosseous (FDI). Bivariate analysis was used to screen for factors associated with disease severity; significant variables were selected for multivariable regression analysis. Older age was associated with higher McGowan grade and diabetes mellitus was associated with unrecordable SNAPs on bivariate analysis. No other variables met inclusion criteria for multivariable regression analysis for McGowan grade or unrecordable SNAPs. Multivariable regression analysis showed older age and higher Distressed Communities Index (DCI) to be associated with decreased motor nerve CVs in ADM. Multivariable regression analysis showed higher body mass index (BMI) and higher DCI to be associated with decreased motor nerve CVs in FDI. No variable was associated with the presence of fibrillations. A subset of patients with cubital tunnel syndrome may benefit from earlier referral for hand surgery evaluation and earlier surgery. Older patients, with higher BMI, with diabetes mellitus, and with economic distress are at higher risk for presentation with more severe disease.

Relieving from Breathlessness in the Wind: A Meta-Analysis and Subjective Report of Effectiveness of Fan Blowing in Patients with Cardiorespiratory Diseases or Cancer.

Breathlessness is common among terminally ill patients with cardiorespiratory disease or cancer. The experience may induce secondary physiological and behavioral responses that limit patient well-being and independence and cause emotional distress. We conducted a meta-analysis on randomized controlled trials (RCTs) that examined the effectiveness of fan blowing on breathlessness among patients with cardiorespiratory diseases or cancer. The PubMed, Cochrane Library, Embase, SCOPUS, and CINAHL databases were searched to retrieve potential articles. The primary outcome was breathlessness severity. The secondary outcomes were SpO2, anxiety, depression, and quality of life. Also, we presented the changes of vital signs and subjective feeling of a male patient who used fan blowing for relieving his breathlessness. Eight RCTs were available for analysis. The pooled results demonstrated no significant difference in breathlessness severity between fan-to-face blowing and control methods (standard mean difference: -0.21, 95% confidence interval: -.59 to .17); however, a significant reduction in breathlessness severity was observed in the short-time intervention compared with long-time intervention. A trend occurred toward significance in the reduction of respiratory rate in fan-to-face blowing compared with control methods (MD: -.64, 95% CI: -1.37 to .09). No differences were observed between groups in oxygen saturation, anxiety, depression, or QoL. The male patient who used fan blowing showed an improved vital signs and a satisfied subjective feeling. Consistent short-time fan-to-face blowing is effective for relieving breathlessness among conscious terminally ill patients with cardiorespiratory diseases or cancer. The use of this convenient method for relieving breathlessness symptoms in terminally ill patients is recommended.

The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps.

Bronchiolitis is the most common cause of hospitalization in infancy and is associated with a higher risk for the development of childhood asthma. However, not all children hospitalized with bronchiolitis will develop asthma. The mechanisms underlying asthma development following bronchiolitis hospitalization are complex. Immune responses to respiratory viruses may underlie both bronchiolitis severity and long-term sequela (such as asthma). Interferons (IFNs) are important components of innate immune responses to respiratory viruses and could influence both asthma development and asthma exacerbations. However, the nature of the relationship between interferon production and wheezing illnesses is controversial. For example, low peripheral blood IFN responses at birth have been linked with recurrent wheeze and asthma development. In contrast, there is evidence that severe illnesses (e.g., hospitalization for bronchiolitis) are associated with increased IFN responses during acute infection (bronchiolitis hospitalization) and a higher risk for subsequent asthma diagnosis. Furthermore, mechanistic studies suggest that bronchial epithelial cells from asthmatic children have impaired IFN responses to respiratory viruses, which may enable increased viral replication followed by exaggerated secondary IFN responses. This review aims to discuss controversies around the role of IFNs as drivers of susceptibility to asthma development following bronchiolitis hospitalization. Past evidence from both mechanistic and cohort studies are discussed. We will highlight knowledge gaps that can inform future research study design.

Immune Repertoire of Sheep Blood B-Cells in the Postvaccination Immune Response

The main specific functions of B-cells are carried out with the help of membrane receptors. Binding of the receptor to its ligand activates a cascade of reactions leading to the formation of memory cells and protective antibodies. The study was conducted to analyze the phenotypic profile of sheep blood B-cells in the process of postvaccination immune response to an inactivated vaccine against pathogens of acute intestinal diseases of animals. Romanov sheep at the age of 1.5 years were immunized twice with a 2-week interval. Studies were conducted before vaccination and on the seventh, 14th, and 21 days of the immune response. The phenotype of B-cells was determined by immunoperoxidase staining using monoclonal antibodies to CD receptors. A simple radial immunodiffusion reaction was used to assess IgG levels. Vaccination of sheep with an inactivated vaccine caused an increase in the level of the general population of leukocytes and a subpopulation of B2 cells (p < 0.05). The absolute number of leukocytes increased on the seventh and 14th days of the primary immune response and on the seventh day of the secondary immune response compared to the initial values. The number of B2 lymphocytes with the CD5 – IgM+ phenotype increased and amounted to 9.0 × 106 cells/mL on day 7 and 11.2 × 106 cells/mL on day 14 of the primary immune response (4.5 × 106 cells/mL before the introduction of the vaccine). An increase in the level of the CD5 – CD19 + IgM + CD20 + lymphocyte subpopulation was noted in the first 2 weeks of the immune response and was 2.5 times higher than the initial value. Data were obtained on the absence of the effect of vaccination on the level of lymphocytes with the CD5 + CD19 + IgM + phenotype (B1-cells), which did not change during either the primary or secondary immune response, which indicates the independence of priming of the two main subpopulations of B-cells. The structural components of the immune system in the process of immunogenesis are not activated simultaneously, and when evaluating the effectiveness of vaccination, functional interrelations of immunological indicators are of particular importance. A strong correlation between the indicators of B2‑cells and the level of total immunoglobulins of class G (r = 0.9) indicates a positive effect of vaccination.

Virtual reality and augmented reality technologies for art education: The perceptions and responses of undergraduate students

The emergent culture of COVID-19 underscored a gap among generations with regard to their responses to new innovations in the education field. This article explores the educational potential of virtual reality (VR) and augmented reality (AR) for the secondary art curriculum through the perspectives and responses of undergraduate art students. The article examines the writing outcomes of a discussion board forum activity that I created to invite the students to share their responses to and reflections on the use of VR/AR technologies in visual art and art education. I share the students’ perspectives on VR/AR use for studio art making under the following three themes: (1) excitement about the new art medium, (2) strengths and risks and (3) educational potential for K–12 curriculum integration. In discussing the students’ reflections, contemporary artists’ use of VR/AR is also explored as a resource for art educators. I end the article by providing suggestions for art educators interested in incorporating VA/AR into their art lessons.

Dyspnea: Common Side Effect.

For dyspnea, standards of care are based on emerging evidence-based practice.&nbsp;Dyspnea, or shortness of breath, is a subjective experience of breathing discomfort marked by distinct sensations of varying intensity. Resulting from interactions among physiologic, psychological, social, and environmental factors, dyspnea may lead to secondary physiologic and behavioral responses. Dyspnea can be caused by cardiac and pulmonary disease (e.g., congestive heart failure, acute coronary syndrome, pneumonia, chronic obstructive pulmonary disease, pulmonary embolism), as well as other conditions (e.g., anemia, mental disorders, lung cancer).

Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury

Macrophage-dominated inflammation by the activation of Toll‐like receptor (TLR) pathway leads to neurological disruption after spinal cord injury (SCI). Regulator of G‐protein signaling 1 (RGS1) is reported to be a regulator in inflammation. The present study thus purposes to identify the unknown role of RGS1 mediating TLR on inflammation post SCI. A mouse model of traumatic SCI was established by a mechanical trauma at T10. The mice underwent SCI and a macrophage line activated by lipopolysaccharide (LPS) were treated with shRNA-RGS1 to elucidate the role of RGS1 in inflammatory progression. The inflammatory factors were measured, and the degree of histology and function protection were determined. The expression levels of RGS1, myeloid differentiation primary response protein 88 (Myd88), (TIR-domain-containing adaptor inducing interferon-β (TRIF), p38, metalloproteinase (MMP)‐2, and MMP‐9 were determined. RGS1 was robustly increased both in LPS-activated macrophage and SCI mice. The TLR signaling pathway-induced inflammation was suppressed by RGS1 knockdown. shRNA‐mediated silence of RGS1 was exhibited a prominent decrease in TNF‐α, IL‐1β and IL-6 via TLR/TRIF/ nuclear factor kappa-B (NF-κB) axis. Depletion of RGS1 also inhibited MMP-induced tissue degradation via MAPK-p38 pathway in SCI mice. Moreover, suppression of RGS1 improved spinal cord histology and function recovery. These findings suggest that RGS1 regulates inflammation and tissue disruption via TLR/TRIF/NF-κB signaling pathway in mice with SCI, thereby explaining a novel target that regulates macrophage inflammation post SCI.