Separate Groups Research Articles

Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3+CD4+CD154+ T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+ T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+ T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Learning Style Preferences of French Learners: A Perspective from Bangladesh

The objective of this research was to determine the learning style preferences of French learners in Bangladesh. A questionnaire was distributed among the French learners in different public universities and two other French language institutes across the country. Reid’s (1984) questionnaire comprises thirty learning style preference items, which are classified into six separate learning styles, i.e., auditory, visual, kinesthetic, tactile, group, and individual styles. The questionnaire is prepared to accumulate quantitative data. The researcher used five questions for the interview to collect the qualitative data. Findings of the survey reveal that visual, group, tactile, and kinesthetic learning styles were determined as major learning styles among the participants of this study. Some recommendations, like using different teaching aids such as audio-video materials and applying different techniques, have been proposed for French learners in Bangladesh. Teacher’s World: Journal of Education and Res arch, 50(1): 155-170

Associations between Adverse Childhood Experiences (ACEs) and Complex-PTSD, moral injury and perceived social support: A latent class analysis

BackgroundAdverse Childhood Experiences (ACEs), including childhood abuse and neglect, are consistently linked to poorer mental health and psychosocial outcomes in adulthood. Complex-posttraumatic stress disorder (C-PTSD) and moral injury are two conditions which can cause significant distress and functional impairment in individuals affected by trauma. However, not much is known about the complex relationships between ACEs, C-PTSD and moral injury. Furthermore, while perceived social support is a commonly cited protective factor for C-PTSD, there is little understanding about how it relates to ACEs in traumatised populations. The aim of this study was to investigate ACEs in a trauma-affected sample of UK military veterans using latent class analysis. Secondly, the study tested for associations between latent classes of ACEs, severity of C-PTSD and moral injury, and levels of perceived social support. MethodData was collected from a UK military veterans mental health charity, from a clinical sample (N = 336) who were receiving treatment for mental health difficulties. Participants completed standardised measures of ACEs, C-PTSD, moral injury, and perceived social support. Data was analysed using a bias-adjusted 3-step approach latent class analysis. Wald statistics were used to test for associations between classes of ACEs and C-PTSD, moral injury and perceived social support. FindingsA two-class model was found to be the best fit for the data, which depicted two classes of ACEs within the sample. The classes showed a distinction between a group of participants who were more likely to endorse experiencing high levels of ACEs, and a separate group who endorsed relatively lower levels of ACEs. As such, the model was interpreted as depicting a low-ACEs (class 1) vs. high-ACEs (class 2) distinction. 56 % of participants fell into class 1 (low ACEs) with 44 % in class 2 (high ACEs). Participants in class 2 (high ACEs) were significantly more likely to score highly for symptoms of C-PTSD and moral injury, and to report lower levels of perceived social support. ConclusionThe present study is the first to report a two-class model of low vs high-ACEs in a clinical sample of UK military veterans. It also describes how membership of the high-ACEs class was significantly associated with higher scores for key mental health and psychosocial variables in C-PTSD, moral injury and perceived social support. The findings have important clinical implications in highlighting the possible role of ACEs in understanding the aetiology of psychopathology in military populations affected by trauma. It also adds to the growing literature which demonstrates how many military personnel experience significant levels of pre-existing trauma and adversity before entering service, and how this can contribute to the development of complex mental health outcomes in adulthood.

Modulation of left ventricular hypertrophy in spontaneously hypertensive rats by acetylcholinesterase and ACE inhibitors: physiological, biochemical, and proteomic studies

BackgroundThe consequences at the molecular level and the mechanisms involved in a possible cardioprotective effect of antihypertensive treatment are not yet fully understood. Here, the efficacy of pyridostigmine (PYR) and trandolapril (TRA) as antihypertensive and antihypertrophic agents was investigated and compared in hypertensive SHR and normotensive WKY rats. In parallel, we investigated the effects of these drugs on myocardial β-adrenergic and cholinergic signaling pathways and protein expression profiles.MethodsAge-matched male SHR and WKY rats were chronically (8 weeks) treated with PYR or TRA in drinking water. Blood pressure (BP) and heart rate (HR) were monitored telemetrically prior to tissue sampling for biochemical analysis. Baroreceptor reflex sensitivity (BRS) and methylatropine HR response as a measure of vagal tone were evaluated in separate groups of animals.ResultsPYR slightly lowered BP and HR in SHR rats during the dark phase of the day, while TRA effectively reduced BP during the light and dark phases without affecting HR. PYR enhanced BRS and improved vagal tone. There were no significant alterations in myocardial β-adrenergic and cholinergic signaling, with the exception of decreased forskolin-stimulated adenylyl cyclase (AC) activity in SHR rats, which was restored by TRA. Proteomic analysis revealed numerous differences induced by both treatments. Notable were changes in TGFβ-related signaling pathways as well as proteins involved in modifying hemodynamic parameters and cardiac hypertrophy.ConclusionsPYR is able to slightly decrease BP and HR in SHR rats but effectively increase BRS through vagal potentiation. The specific differences in protein expression profiles in rat myocardium induced by treatment with PYR and TRA reflect different mechanisms of action of these two agents at the molecular level.

Assessment of suitability of the Dniester River's water for drinking water supply

The Dniester is a transboundary river between Ukraine and the Republic of Moldova. It is the second longest river in Ukraine and the ninth in Europe. From its source to a town of Staryi Sambir, the Dniester flows through the Carpathian Mountains, then across the flat territory of Ukraine and Moldova. The Dniester Basin extends across seven regions in southwestern Ukraine (Lviv, Ivano-Frankivsk, Ternopil, Khmelnytskyi, Vinnytsia, Chernivtsi and Odesa Regions). A small area of the river in its upper reaches is located in Poland. The basin's shape is a very elongated oval that is curved in the middle, about 700 km long with an average width of 120 km. As it flows into the Black Sea, the Dniester River forms the Dniester estuary in Odesa region (between Ovidiopol and Bilhorod-Dnistrovskyi districts). The estuary area of the Dniester River is a complex landscape system at the sea-river-land contact. Drinking water is an important factor determining a person's health. Due to the intensive development of industry, agriculture and utility services, the number of pollutants that enter the environment and worsen the quality of drinking water in Ukraine keeps increasing. This increases the risk of toxic and infectious diseases spread among the population that consumes such low-quality water. That is why solving the problem of drinking water monitoring and assessment of its quality is a pressing task requiring urgent action. The article examines the quality of water for drinking needs at the water intake site of the Dniester River, a town of Biliaivka, for 2018-2022. Water quality assessment was carried out according to DSTU 4808: 2007 based on average and worst values. The methodology covers 80 indicators and, in accordance with sanitary legislation, is divided into seven separate groups (blocks). According to hygienic standards, the quality of river water is considered suitable for use if it belongs to quality classes 1-3. In this research, the analysis was carried out according to 23 indicators included in three groups, so the assessment is considered as tentative: Group I - organoleptic indicators (chromaticity, turbidity); Group II - general sanitary indicators (dry residue (mineralization), sulfates, chlorides, magnesium, alkalinity, hydrogen index, ammonium nitrogen, nitrite nitrogen, nitrate nitrogen, phosphate phosphorus, dissolved oxygen, bichromate oxidation (COD), BSK5); Group VII – toxicological parameters (total iron, manganese, chromium (VI), zinc, petroleum products, synthetic surface active agents (surfactants), volatile phenols). It was determined that, according to the average values, the water quality of the Dniester at the water intake site is characterized as "good", which means it has clean water of acceptable quality. As for the worst indicators, the water was assessed as transitional in quality from "good" (clean) to "satisfactory" (slightly polluted).

Abstract A025: Cell of origin does not underlie transcription heterogeneity in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) it though to develop through induction of different precursor lesions, however, the normal cell type that gives rise to these precancerous lesions and PDAC is unclear. Recent studies using mouse models and ex vivo cultured human cells suggest that the cellular origin of PDAC may be either acinar or ductal cells. Potential transcriptional markers associated with PDAC of different cellular origins have been identified. Here, we interrogate whether these markers are predictive of cellular of origin across models using mouse models where acinar and ductal cells (Ptf1aCreER or Sox9CreER) expressing oncogenic Kras in the absence of Trp53 or Pten give rise to PDAC tumors. We found that acinar- and ductal-cell-derived PDAC exhibit transcriptional differences both in vivo and in vitro when comparing within one genotype or sample source type (e.g. bulk tumor or primary cell lines). However, previously predicted markers of cellular origin had variable expression across models and sample types suggestive of differences specific to those sample sets. Using our larger sample sets and multiple genotypes and source types, we proposed a more comprehensive set of cell of origin markers for consideration. Application of these markers to our own data sets, however, failed to properly segregate acinar- and ductal-cell-derived PDAC into separate groups. This suggests that the transcriptional heterogeneity observed in our sample set was not driven by the tumors arising from different cellular origins. We also examined the relationship between cell of origin and patient PDAC transcriptional subtypes using our mouse model datasets. Our findings support previous research indicating that mouse models of acinar-cell-derived PDAC favor those of a classical subtype. However, our mouse PDAC samples all express similar or very low levels of the genes denoting the basal subtype, suggesting that the basal subtype was not strongly present in any of the datasets we examined. In summary, our data suggest that acinar and ductal cells converge into a very similar PDAC transcriptional state and that, if differences can be identified, they will likely be identified by non-transcript based readouts. Citation Format: Ken Chu, Alex Lee, Karnjit Sarai, Yan Dou, Wesley Hunt, Emma Croft, Atefeh Samani, Farnaz Taghizedeh, Claire Dubois, Stephane Flibotte, Janel Kopp. Cell of origin does not underlie transcription heterogeneity in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A025.

On determining of the protograph features based on the graphic-orthographic systems of manuscripts

This article is concerned with the study of medieval manuscripts and the determining of the features of protographs based on the graphic and orthographic systems of their scribal copies. The study involves three manuscripts created in Nuremberg in the 15th century. The texts of the mentioned manuscripts are copies from the first two complete translations of one of the medieval treatises. Based on the study of the graphic and orthographic systems of these texts, as well as some of their morphological features, the author of the article makes an attempt to establish the relationship between the texts under study, as well as to restore some of the features of their protographs. The sources of influence on the formation of the graphic and orthographic portrait of the scribe were identified as a result of the study of the graphic and orthographic features of the texts. Among them the author identifies the written tradition of the scriptorium, features of the local dialect and dialect areas, as well as characteristic features of the protograph. A separate group includes such a source of variability as the individual preferences of the scribe. Analysis of the graphic and orthographic portrait of each of the scribes who participated in the creation of the texts under study allows us to determine the approximate time and place of creation of the protograph, as well as changes characteristic of each stage of conscious processing of the text. As a result of the study, a diagram was drawn up that clearly demonstrates the relationships between the texts under study.

Genetic parameters and genotype-by-environment interaction estimates for growth and feed efficiency related traits in Chinook salmon, Oncorhynchus tshawytscha, reared under low and moderate flow regimes

BackgroundA genotype-by-environment (G × E) interaction is defined as genotypes responding differently to different environments. In salmonids, G × E interactions can occur in different rearing conditions, including changes in salinity or temperature. However, water flow, an important variable that can influence metabolism, has yet to be considered for potential G × E interactions, although water flows differ across production stages. The salmonid industry is now manipulating flow in tanks to improve welfare and production performance, and expanding sea pen farming offshore, where flow dynamics are substantially greater. Therefore, there is a need to test whether G × E interactions occur under low and higher flow regimes to determine if industry should consider modifying their performance evaluation and selection criteria to account for different flow environments. Here, we used genotype-by-sequencing to create a genomic-relationship matrix of 37 Chinook salmon, Oncorhynchus tshawytscha, families to assess possible G × E interactions for production performance under two flow environments: a low flow regime (0.3 body lengths per second; bl s−1) and a moderate flow regime (0.8 bl s−1).ResultsGenetic correlations for the same production performance trait between flow regimes suggest there is minimal evidence of a G × E interaction between the low and moderate flow regimes tested in this study, for Chinook salmon reared from 82.9 ± 16.8 g (x¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\overline{\ ext{x}}}$$\\end{document} ± s.d.) to 583.2 ± 117.1 g (x¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\overline{\ ext{x}}}$$\\end{document} ± s.d.). Estimates of genetic and phenotypic correlations between traits did not reveal any unfavorable trait correlations for size- (weight and condition factor) and growth-related traits, regardless of the flow regime, but did suggest measuring feed intake would be the preferred approach to improve feed efficiency because of the strong correlations between feed intake and feed efficiency, consistent with previous studies.ConclusionThis new information suggests that Chinook salmon families do not need to be selected separately for performance across different flow regimes. However, further studies are needed to confirm this across a wider range of fish sizes and flows. This information is key for breeding programs to determine if separate evaluation groups are required for different flow regimes that are used for production (e.g., hatchery, post smolt recirculating aquaculture system, or offshore).

Phytoplankton communities quantified from hyperspectral ocean reflectance correspond to pigment-based communities

Community detection analysis is a powerful tool to separate groups of samples that are similar based on their composition. Here, we use a paired global dataset of in-water hyperspectral remote sensing reflectance (Rrs) spectra and high-performance liquid chromatography (HPLC) pigment concentrations to investigate the similarity in phytoplankton composition of the communities detected from each method. Samples were separated into optical communities using network-based community detection analysis applied to the Rrs residual (δRrs), which is calculated by subtracting a modeled hyperspectral Rrs spectrum from a measured hyperspectral Rrs spectrum. The δRrs spectrum accentuates short spectral scale features (<=10 nm) that should be related to phytoplankton pigment composition metricsTo test whether these optical communities correspond to phytoplankton communities, we also used network-based community detection analysis to separate HPLC pigment-based communities from twelve accessory pigment ratios to total chlorophyll-a. Our results demonstrate that three distinct phytoplankton communities can be separated from both hyperspectral Rrs data and HPLC pigment data and that a majority of these samples (74%) were assigned to the same communities. Differences in community assignment were also identified and potential sources for discrepancies were discussed. Importantly, the optical communities assigned here offer a new tool for assessing phytoplankton community composition on global scales using hyperspectral Rrs observations, such as those provided by the Ocean Color Instrument (OCI) on NASA’s new Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) satellite.

PENGARUH PENYULUHAN GIZI DENGAN MEDIA GAME EDUKASI BERBASIS ANDROID TERHADAP KONSUMSI BUAH DAN SAYUR

The main issue faced in fruit and vegetable consumption is that, on a national scale, the consumption of fruits and vegetables by the Indonesian population is still below the recommended levels. In the context of increasing needs for nutritional and health understanding, this study aimed to examine the effect of an android-based educational game on fruit and vegetable consumption through teacher capacity enhancement among junior high school students in Ngabang, Landak Regency. A quasi-experimental method utilizing the separate sample pretest-posttest control group design was employed with two treatment groups. The sample consisted of 35 Grade 8 students for each group. The sampling technique used quota sampling. Statistical analysis using paired t-test and independent t-test. The results indicate there was no significant difference in fruit consumption frequency between the control group before and after the intervention (p=0.160), whereas a significant difference was observed in the treatment group (p=0.000). Similar patterns were observed for vegetable consumption frequency, with no difference in the control group (p=0.263) but a significant difference in the treatment group (p=0.000). Overall, the study found a significant difference in the frequency of consumption between the control and treatment groups for both fruits (p=0.000) and vegetables (p=0.000). This suggests that the android-based educational game, through enhancing teacher capacity, effectively increases fruit and vegetable consumption among junior high school students. These findings highlight the potential of using educational technology to improve dietary habits and address nutritional issues among adolescents in Indonesia.

Protocol for a tailored self-compassion program for peer mentors within Canadian Spinal Cord Injury community service organizations

ObjectiveIndividuals who serve as peer mentors within Canadian spinal cord injury (SCI) community service organizations are reporting compassion fatigue from their roles. One psychological resource that has the potential to reduce compassion fatigue and promote overall mental health among peer mentors is self-compassion. However, there is limited knowledge of any self-compassion programs that have been tailored to address the needs of these individuals. To address this limitation, this paper outlines a protocol to examine the feasibility, acceptability, implementation, and effectiveness of a tailored self-compassion program to reduce compassion fatigue and enhance compassion satisfaction, self-compassion, and mental health among peer mentors within Canadian SCI community service organizations.DesignThe 6-week online program will be tested among 20 individuals (five separate groups of four) who serve as peer mentors within two Canadian SCI community service organizations.MethodFeasibility and implementation data will be collected throughout the duration of the program and post program while acceptability data will be collected post program. To evaluate the effectiveness of the program, we will follow a single-group quasi-experimental design with surveys (pre/post/follow-up) and semi-structured interviews (post/follow-up).ResultsResults from this study are intended to inform the design of a self-compassion program for peer mentors within Canadian SCI community service organizations who experience compassion fatigue and reduced mental health.ConclusionProviding evidence for the effectiveness of this program could prove useful for Canadian SCI community service organizations who wish to better support and retain their peer mentors and thus improve the quality of support they provide to mentees.

Subclass IId bacteriocins targeting mannose phosphotransferase system-Structural diversity and implications for receptor interaction and antimicrobial activity.

The bacterial mannose phosphotransferase system (Man-PTS) mediates uptake of selected monosaccharides. Simultaneously, it is a receptor for diverse bacteriocins such as subclass IIa pediocin-like bacteriocins and some subclass IId ones (garvicins ABCQ, lactococcins ABZ, BacSJ, ubericin K, and angicin). So far, no attempt has been made to categorize this ever-expanding group of bacteriocins. Here, we identified Man-PTS as a receptor for a number of previously uncharacterized bacteriocins, and demonstrated that they all belong to a large family of Man-PTS-binding nonpediocin-like peptides, providing new insights into their structure and function. Based on amino acid sequence similarities between members of this family, we propose their classification into five groups. This classification conveniently distinguishes bacteriocins with specific structures and properties regarding their spectrum of antimicrobial activity and pattern of interaction with Man-PTS. With respect to the latter, we indicate individual amino acid residues or regions of Man-PTS and the bacteriocin responsible for their interaction. In Man-PTS, these residues localize to the exterior of the transport complex, specifically the extracellular loop of the so-called Vmotif domain-containing regions γ and/or γ+, and to the interior of the transport complex, specifically the interface between the Core and Vmotif domains. Finally, we propose that while the bacteriocins from separate groups display specific binding patterns to Man-PTS, the general mechanism of their interaction with the receptor is universal despite significant differences in their predicted structures, i.e. after initial docking on the bacterial cell through an interaction with the Man-PTS regions γ and/or γ+, they pull away its Core and Vmotif from one another to form a pore across the membrane.

The Relationship Between the Modified Glasgow Prognostic and SYNTAX Scores in Patients with Non-ST Elevation Myocardial Infarction.

This study investigated the modified Glasgow prognostic score (mGPS) to determine its predictive value and how it could be compared with various inflammatory markers, including C-reactive protein (CRP) to albumin ratio and neutrophil-to-lymphocyte ratio, for determining the extent and severity of coronary artery disease (CAD) in patients with non-ST-elevated myocardial infarction (NSTEMI). This study analyzed the cases of 295 patients with NSTEMI who had undergone coronary angiography. In an effort to determine the seriousness and scope of CAD in each patient, the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score was calculated and then assessed. The study sample was divided into two separate groups based on the SYNTAX score: moderate to high SYNTAX (>22) and low SYNTAX (≤22). There were 295 patients (23.1% female, 76.9% male) included in the research, with an average age being 61.2±10.9 years, and the mean SYNTAX score being 7.3±10.4 (range: 0-40). Those with a SYNTAX score >22 were observed to possess significantly higher levels of CRP, CRP/albumin ratio, and mean mGPS 1-2 ratios compared with those with a SYNTAX score ≤22 (all p<0.001). Smoking [odds ratio (OR): 3.341, 95% confidence interval (CI): 1.531-7.294; p=0.002], CRP/albumin ratio (OR: 4.958, 95% CI: 1.335-18.418; p=0.017), and mGPS score of 1-2 (OR: 3.121, 95% CI: 1.430-6.814; p=0.004) were independent factors used to help predict a high SYNTAX score. It seems possible to make use of the mGPS when estimating the degree and intricacies of CAD in patients with NSTEMI, as there appears to be a connection with higher SYNTAX scores.

Generating pathways to domestically sourced plasma-derived medicinal products: Report from a workshop by the International Plasma and Fractionation Association and the Working Party on Global Blood Safety of the International Society of Blood Transfusion.

Plasma-derived medicinal products (PDMPs) are recognized internationally as essential medicines required to treat various acute and chronic conditions including congenital deficiencies of plasma proteins in haemophilia and primary immune deficiency. Global provision of these medicines is dominated by a small number of commercial companies, influencing the price and availability of the products. Achieving a level of strategic independence from this dominance is now seen as a public health priority in many countries. During the Regional Congress of the International Society for Blood Transfusion (ISBT) in Cape Town, South Africa, in November 2023, around 50 delegates from 24 countries participated in a workshop (WS) organized jointly by the International Plasma and Fractionation Association (IPFA) and the ISBT Working Party on Global Blood Safety on pathways towards provision of PDMPs from domestic plasma independent of commercial purchase in the open market. The WS was structured around three themes, each addressed by a separate group: Quality/safety requirements for plasma for fractionation (PfF) Stepwise access for safe plasma proteins Approaching contract fractionation A synthesis of conclusions from these groups included the following: The need to acquire support from government authorities for a national plasma policy, recognizing the difficulties posed by unstable political and bureaucratic environments. The value of embedding plasma and PDMPs within a patient blood management (PBM) paradigm to promote optimal clinical use of PDMPs. Training of blood/plasma collection personnel in the relevant principles of Good Manufacturing Practice (GMP), coupled with regulatory oversight of plasma product production in the engaged jurisdictions. Appreciation that limited access to contract fractionation may necessitate a stepwise approach, which may include small-scale preparation of versions of essential plasma proteins as an intermediate phase towards the manufacture of industrial-scale PDMPs from domestic plasma.

Modulatory Potential of Selenium Supplementations on the Growth, Nutrients Profile and Regulation of Antioxidant Status of Striped Catfish (Pangasius Hypophthalmus)

This study is designed to evaluate the impact of varying selenium levels on growth potential, nutrient profile and antioxidant enzymes activity in striped catfish. Fish were randomly allocated into 15 circular indoor tanks, each with a capacity of 2000 L, (100 (H) x 200 cm (D)) dimension, and were raised for 12 weeks. Fifteen fish were allocated to each tank across four separate treatment groups, each replicated three times, following an entirely randomized design. Five iso-nitrogenous diets (30% CP) were prepared from basal diet in which one was control and other four were supplemented selenomethionine (Se-met) with levels of 0, 0.5, 1.0, 1.5 and 2.0 mg/kg. Upon completion of the feeding trial, a diet containing Se at 1.5 mg/kg resulted in a significant increase (P&lt;0.05) in weight gain (229.60±3.00) and SGR (0.92±0.23), along with a lower FCR (2.18±0.32). While, proximate composition remains non-significant (P &gt; 0.05) against dietary Se feed. Antioxidant enzymes activity in liver and muscle found higher in Se1.5 diet and Se2.0 mg/kg diet in comparison to lower dietary Se treatments. Moreover, dietary Se1.5 and Se2.0 treatments values remained non-significant. Overall, the results indicated that the incorporation of Se-met at 1.5 mg/kg in the diet can improve growth performance and antioxidant status in P. hypophthalmus.

Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder

BackgroundFunctional magnetic resonance imaging studies examining cue reactivity in cannabis use disorder (CUD) either have had small sample sizes or have involved non–treatment-seeking participants. As a secondary analysis, we administered a functional magnetic resonance imaging cue-reactivity task to participants with CUD enrolled in 2 separate clinical trials (varenicline or repetitive transcranial magnetic stimulation) to determine the task activation patterns for treatment-seeking participants with CUD. We aimed to determine the activation patterns for the total sample and behavioral correlates. We additionally compared studies to determine if patterns were consistent. MethodsTreatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline using the Marijuana Craving Questionnaire–Short Form and completed a visual cannabis cue-reactivity task during functional magnetic resonance imaging (measuring the blood oxygen level–dependent response) following 24 hours of cannabis abstinence. ResultsThe sample included 65 participants (n = 37: varenicline trial; n = 28: repetitive transcranial magnetic stimulation trial; 32% female; mean age = 30.4 ± 9.9 years). When comparing cannabis images versus matched neutral images, participants showed greater blood oxygen level–dependent response in bilateral ventromedial-prefrontal, dorsolateral-prefrontal, anterior cingulate, and visual cortices as well as the striatum. There was stronger task-based functional connectivity between the medial prefrontal cortex and both the amygdala and the visual cortex. Craving negatively correlated with blood oxygen level–dependent response in the left ventral striatum (R2 = −0.32; p = .01) in the full sample. There were no significant differences in either activation or task-based functional connectivity between studies. ConclusionsIn 2 separate treatment-seeking groups with CUD, there was increased cannabis cue reactivity and task-based functional connectivity in regions related to executive function and reward processing. Cannabis craving was negatively associated with cue reactivity in the left ventral striatum.

Same versus separate sessions of endoscopic ultrasound-guided fine-needle biopsy and endoscopic retrograde cholangiopancreatography for distal malignant biliary obstruction: a propensity score-matched study

ABSTRACT Background Same-session endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) is an attractive policy for patients with distal malignant biliary obstruction (DMBO) requiring fine-needle biopsy (FNB) and biliary drainage. However, scanty and conflicting data exists regarding safety and efficacy when comparing these two procedures performed in same versus separate sessions. Methods Single-center, retrospective, propensity score-matched study including patients with DMBO who underwent EUS-FNB followed by ERCP during the same or separate sessions. The primary outcome was the safety of the procedure [number of patients experiencing adverse events (AEs), overall AEs, its severity, post-ERCP pancreatitis (PEP)]. Secondary outcomes were successful ERCP, use of advanced cannulation techniques, EUS-FNB adequacy, length of hospital stay, overall procedure time, and time to recurrent biliary obstruction. Results After propensity matching, 87 patients were allocated to each group. AEs developed in 23 (26.4%) vs. 17 (19.5%) patients in the same and separate sessions group, respectively (p = 0.280). The overall number, the severity of AEs, and the rate of PEP were similar in the two groups. Secondary outcome parameters were also comparable in the 2 groups. Conclusions Same-session EUS-FNB followed by ERCP with biliary drainage is safe and does not impair technical outcomes of tissue adequacy and biliary cannulation.

Abstract P231: Self-administration of Remifentanil Induces Endothelial Dysfunction in Thoracic Aorta and Impaired Cavernosal Reactivity of Wistar Rats

Aims: Recent studies have implicated the use of prescription opioids as a risk factor for cardiovascular diseases (CVD), with associations including myocardial infarction, coronary artery disease and vascular deterioration. Further, opioid-dependent patients show increased vascular aging and arterial stiffness when compared to opioid-naïve controls. Our hypothesis was that rats dependent on remifentanil (a fentanyl analog) after a 12-day operant self-administration (SA) study lead to vascular dysfunction in thoracic aorta. Because erectile dysfunction (ED) is associated with arterial stiffness and is positively correlated with its severity, we hypothesized that opioid SA impaired corpus cavernosum (CC) reactivity as well. Methods: Male Wistar rats (12 weeks-old) were implanted with intravenous catheters and learned to lever press (FR1) for remifentanil (1µg/kg/infusion). A separate group of rats received passive yoked infusions of saline administered in synchrony with remifentanil-treated animals to control volumetric vascular effects. Following administration, animals were euthanized, and aorta and CC collected to evaluate function using both pin and strip myographs. Concentration-response curves to phenylephrine (Phe; 10 -11 -10 -4 M), sodium nitroprusside (SNP) and acetylcholine (Ach or SNP; 10 -10 -10 -4 M) were performed to test contractility and endothelium-independent and -dependent relaxation respectively. Results: Remifentanil-treated rats showed rapidly acquired SA behavior, exhibiting robust and selective drug-paired lever pressing when compared to the non-drug paired lever. In contrast, yoked saline-treated controls rarely exhibited lever pressing. Endothelium-dependent relaxation in the aorta was diminished in the remifentanil group (Rmax: Control: 68.7±2.7 vs. Remi: 47.8±3.7%; p&lt;0.05). There were no observed alterations in endothelium-independent relaxation or vascular contraction. However, CC contraction was slightly shifted to the right in remifentanil treated rats (pEC 50 : Control: 6.04±0.09 vs. Remi: 5.66±0.12; p&lt;0.05). No changes were observed in the CC relaxant response. These findings indicate that 12 days of remifentanil administration results in endothelial dysfunction in large arteries and impaired cavernosal reactivity. Long-term exposure may lead to aortic stiffness exacerbating ED severity and increases in pulse-wave velocity in opioid-dependent patients contributing to the onset of hypertension.

Abstract P160: Sex Differences in Age-Dependent Hypertension and Cognitive Impairment in Sprague-Dawley Rats

Objective: We previously found that male (M), but not female (F), Sprague-Dawley (SD) rats develop age-dependent hypertension (HTN) that is associated with cognitive impairment. We hypothesized that ovariectomy (OVRX) at midlife, to model human menopause, would induce hypertension and cognitive impairment with age. Methods: In M and F SD rats at 3-, 8-, and 16-months-old (MO), blood pressure (MAP; mmHg) and sympathetic tone to the vasculature (iv hexamethonium, PeakΔMAP; mmHg) was measured via femoral artery cannulation. Recognition memory was assessed using the novel object recognition task. Blood brain barrier (BBB) integrity in the PVN was assessed as FITC extravasation following carotid artery cannulation. In a separate group of female rats at 8 MO, sham procedure, OVRX, or OVRX with estradiol replacement for 8-months (s.c. estradiol valerate, 1.5 mg extended-release pellet) was performed and rats were aged to 16MO. At 16MO, the previously described procedures were carried out. Results: M, but not F, SD rats develop age-dependent HTN and increased sympathoexcitation that is associated with recognition memory deficits and BBB disruption. Following OVRX, female rats develop age-dependent HTN that is associated with recognition memory deficits and BBB disruption. Replacement of estrogen with 17β-estradiol prevented the development of HTN, cognitive impairment, and BBB disruption. Conclusions: In males, HTN induces BBB disruption and is associated with cognitive impairment. Our studies suggest midlife loss of estrogen likely contributes to the development of age-dependent HTN and cognitive impairment in females. We speculate estrogen supplementation may mitigate HTN-related changes in memory with age.

Abstract 21: The Detrimental Effects of a Comorbidity of Increased Blood Pressure Variability and High Salt Diet on Cardiovascular and Neurovascular Outcomes

Recent studies have identified increased blood pressure variability (BPV) as a novel risk factor for cognitive decline, independently from absolute BP values. However, the underlying mechanisms are poorly defined. In addition, whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is not known. We tested the hypothesis that vascular damage resulting from blood pressure fluctuations in BPV disrupts critical mechanisms regulating cerebral blood flow (CBF), impairing perfusion and leading to neurovascular dysfunction and cognitive decline. We established a murine BPV model and evaluated the impact of BPV on systemic BP (baroreceptor reflex) and CBF regulation (myogenic and functional hyperemia (FH) responses). Mice were implanted with a cranial window for in-vivo two-photon (2P) imaging. A programmable pump infused 6-8 pulses/day of angiotensin II ((Ang II 18 µg/day) (BPV) or saline (Control) for 25 days, and cardiovascular variables were measured via DSI telemetry. Ang II pulse infusions evoked transient BP increases (Δ43±4 mmHg, MAP; P&lt;0.01,n=8); however, did not induce hypertension in the BPV group. BPV mice displayed increased BPV index (P=0.04,n=12) and cognitive decline (novel object recognition test (P=0.01,n=10)). Telemetry data showed a decrease in bradycardic responses following chronic BPV (P=0.03, n=8). Data from 2P studies showed enhanced myogenic response in parenchymal arterioles of BPV vs Controls (P&lt;0.01,n=9-15 runs) when BP transitions from low to high BP. We observed a blunted FH in BPV vs Control during low BP (P&lt;0.01,n=6-7). During high BP, FH was pronounced in Controls (P&lt;0.01,n=6-7); however, pressure-induced vascular responses were abolished in BPV mice (P&lt;0.01,n=6-7). In separate groups of mice, the Control and BPV protocol was repeated with all mice receiving a high-salt diet (HS; 4% NaCl chow+1% NaCl drinking water: Control+HS or BPV+HS). There were no changes in 24-hr MAP in Control+HS (P&gt;0.85, n=5). Whereas BPV+HS mice developed sustained hypertension (increased 24-hr MAP; P&lt;0.01, n=4). These data demonstrate that BPV alters mechanisms regulating CBF and BP, contributing to cognitive decline and that HSD may exacerbate the detrimental effects of BPV on BP regulating mechanisms. Ongoing studies are examining the comorbid effects of BPV+HS on the cerebrovasculature and direct CBF changes in BPV and BPV+HS mice.