Human Studies Research Articles

Ticagrelor modestly raises plasma riboflavin concentration in humans and inhibits riboflavin transport by BCRP and MRP4.

Riboflavin (vitamin B2) has been proposed as a biomarker for breast cancer resistance protein (BCRP) activity. In recent studies in mice, cynomolgus monkeys, and humans, BCRP-inhibiting drugs increased the plasma concentration of riboflavin. We showed recently that ticagrelor inhibits BCRP and raises the plasma concentrations of the BCRP substrate rosuvastatin in healthy volunteers. In the same drug-drug interaction study, we now investigated whether ticagrelor affects the plasma concentrations of riboflavin. Intake of 90 mg ticagrelor increased the ratio between the peak plasma riboflavin concentration and the fasting riboflavin concentration before ticagrelor administration by 1.20-fold (90% confidence interval, 1.10-1.32; P = 0.006) compared to placebo. In vitro, riboflavin was transported by BCRP and multidrug-resistance-associated protein 4 (MRP4) but no clear transport was observed by MRP2, MRP3, or the P-glycoprotein. Moreover, ticagrelor inhibited the transport of riboflavin in BCRP- and MRP4-expressing membrane vesicles with unbound 50% inhibitory concentrations of 0.020 and 1.1μM, respectively. Based on vesicle and tissue protein expression data, the small intestinal MRP4-mediated efflux clearance of riboflavin (1.2-1.4 nL/min/mg) was estimated to be similar to that mediated by BCRP (0.23-1.3 nL/min/mg). As MRP4 is expressed in the basolateral membrane of enterocytes, it may facilitate the absorption of riboflavin and impair the utility of riboflavin as a biomarker of intestinal BCRP. To conclude, ticagrelor modestly raises the plasma concentration of riboflavin probably by inhibiting intestinal BCRP. Inhibition of intestinal MRP4 may have reduced the absorption of riboflavin and limited the effect of ticagrelor on riboflavin levels.

Probiotics as an Adjunct Approach to the Prevention and Treatment of Colon Cancer: A Review

Abstract:: One out of every six people in the world is suffering from cancer disease. The major causes of cancer are high consumption of tobacco, high body mass index, and alcoholic beverages with low intake of a healthy diet and limited physical activity. Colon cancer is one of the leading causes of cancer-related morbidity worldwide. In the past few years, probiotics have drawn a lot of interest as potential preventive and therapeutic anticancer agents. This literature review addressed both human and animal research that has explored the association between probiotics and colon cancer. Probiotic administration has remarkable potential for the prevention and treatment of colon cancer through various mechanisms such as inhibiting the growth of cancer cells via apoptosis, improving immune activity, restoring gut microbiota, improving intestinal barrier properties, synthesizing anticarcinogenic compounds, and degrading carcinogenic compounds. Therefore, probiotics emerge as an adjunct therapy, holding the potential to significantly reduce the risk of colorectal cancer.

Novel 3D printed capsule to work as an auxiliary for enteric-coating for gastroprotective drug delivery system.

In the current research work, 3d printed capsules were printed by using FDM based 3D printer. A model drug punched into matrix tablets was put inside and encapsulated in the capsule. It was compared with the highly advanced ready-to-fill enteric-coated capsule Eudracap™ capsule. Solid Works and slicing software were used to design and cast off the shape of the capsule shell. The design of the cap and body was made and capsules were printed accordingly. All were evaluated for acid uptake and disintegration tests. In an acidic medium at pH 1.2, it has not been disintegrated or opened. While in the intestinal pH at 6.8 body and cap got separated after 45 ± 05 min. All sizes of capsules were also assessed for dosage form they can uphold. This could be a good option for customized drug delivery for human and animal studies.

Psychopharmacological Treatment of Depression and Anxiety and their Different Drug Delivery Targets

Abstract: General practitioners observe a high prevalence of anxiety and depression symptoms. Depressed or anxious patients frequently develop both conditions. The symptoms of both diseases may be present at the same time. There has been numerous studies on higher levels of depression, bipolar disorder II, and mixed depression. So, we ended up reviewing different drug delivery targets. Even at low dosages, antidepressants were better absorbed and were more effective when given by the nose. In this review, we focused on cutting-edge methods for intranasal antidepressant delivery vehicles. Consequently, it seems that drugs that are sufficiently effective, have fewer side effects, and are less expensive. The researchers in this metaanalysis set out to determine whether or not they have been used successfully in traditional medicine to treat depression in human or animal studies.

High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step

Experimental autoimmune encephalomyelitis (EAE) is a model for central nervous system (CNS) autoimmune demyelinating diseases such as multiple sclerosis (MS) and MOG antibody-associated disease (MOGAD). Immunization with the extracellular domain of recombinant human MOG (rhMOG), which contains pathogenic antibody and T cell epitopes, induces B cell-dependent EAE for studies in mice. However, these studies have been hampered by rhMOG availability due to its insolubility when overexpressed in bacterial cells, and the requirement for inefficient denaturation and refolding. Here, we describe a new protocol for the high-yield production of soluble rhMOG in SHuffle cells, a commercially available E. coli strain engineered to facilitate disulfide bond formation in the cytoplasm. SHuffle cells can produce a soluble fraction of rhMOG yielding >100 mg/L. Analytical size exclusion chromatography multi-angle light scattering (SEC-MALS) and differential scanning fluorimetry of purified rhMOG reveals a homogeneous monomer with a high melting temperature, indicative of a well-folded protein. An in vitro proliferation assay establishes that purified rhMOG can be processed and recognized by T cells expressing a T cell receptor (TCR) specific for the immunodominant MOG35–55 peptide epitope. Lastly, immunization of wild-type, but not B cell deficient, mice with rhMOG resulted in robust induction of EAE, indicating a B cell-dependent induction. Our SHuffle cell method greatly simplifies rhMOG production by combining the high yield and speed of bacterial cell expression with enhanced disulfide bond formation and folding, which will enable further investigation of B cell-dependent EAE and expand human research of MOG in CNS demyelinating diseases.

HOIMotion: Forecasting Human Motion During Human-Object Interactions Using Egocentric 3D Object Bounding Boxes.

We present HOIMotion - a novel approach for human motion forecasting during human-object interactions that integrates information about past body poses and egocentric 3D object bounding boxes. Human motion forecasting is important in many augmented reality applications but most existing methods have only used past body poses to predict future motion. HOIMotion first uses an encoder-residual graph convolutional network (GCN) and multi-layer perceptrons to extract features from body poses and egocentric 3D object bounding boxes, respectively. Our method then fuses pose and object features into a novel pose-object graph and uses a residual-decoder GCN to forecast future body motion. We extensively evaluate our method on the Aria digital twin (ADT) and MoGaze datasets and show that HOIMotion consistently outperforms state-of-the-art methods by a large margin of up to 8.7% on ADT and 7.2% on MoGaze in terms of mean per joint position error. Complementing these evaluations, we report a human study (N=20) that shows that the improvements achieved by our method result in forecasted poses being perceived as both more precise and more realistic than those of existing methods. Taken together, these results reveal the significant information content available in egocentric 3D object bounding boxes for human motion forecasting and the effectiveness of our method in exploiting this information.

Biopsychosocial Health Considerations for Astronauts in Long-Duration Spaceflight: A Narrative Review.

Long-duration spaceflights beyond low-Earth orbit, including missions to the Moon and Mars, pose significant health risks. Although biomedical approaches commonly appear in the literature, considering psychological and social factors alongside physiologic health offers a more holistic approach to astronaut care. Integrating the biopsychosocial (BPS) framework into medical planning addresses complex spaceflight challenges and aids in developing mitigation strategies. This review examined health risks associated with long-duration spaceflight within a BPS framework. Sources included governmental space agencies, academic textbooks, and relevant publications from multiple databases. Considering the National Aeronautics and Space Administration's Human Research Program's 5 main hazards, a conceptual model was developed to highlight the multifactorial BPS effects of spaceflight. In space, astronauts face unique environments and biological adaptations, including fluid shift, plasma volume loss, bone density loss, and muscle atrophy. Noise and the absence of natural light disrupt circadian rhythms, causing sleep disturbances and fatigue, which affect physical and mental health. Studies on crews in isolated and confined extreme environments reveal psychosocial challenges, including impaired mood and cognition, interpersonal tension, and miscommunication. International collaboration in spaceflight introduces differences in communication, problem solving, and social customs due to diverse cultural backgrounds. Upcoming long-distance missions likely will amplify these challenges. This review emphasizes BPS health considerations in long-duration spaceflight. It highlights the interplay among psychological, social, and biological factors, advocating for multidisciplinary teams and a holistic approach to astronaut health and mission planning and the potential added value of BPS perspectives in considering countermeasures.

Barriers and hurdles delaying governance approval for an ethically approved nationwide clinical trial in pancreatic cancer.

Streamlined, expedited clinical research is fundamental to rapidly test, translate and implement novel treatments into routine care to improve patient outcomes. The National Mutual Acceptance (NMA) scheme was designed to expedite the ethics approval process, however, growing concerns exist about the fragmented time-consuming governance process needed to actually commence clinical research in Australia. This study reports hurdles and barriers encountered while seeking governance approval for the SCANPatient trial. SCANPatient is a nationwide multi-centre trial comparing standard narrative radiological reporting of CT scans for suspected pancreatic ductal adenocarcinoma. with an alternative structured approach. SCANPatient was approved by a national Human Research Ethics Committee under the NMA. The documents, time, costs and platforms required to obtain governance approval and open the trial at 30 participating hospitals were analysed. Wide variation exists in research governance office (RGO) requirements for local approval, resulting in extra costs (>$117 000), delays of up to 4 months in commencing the trial at some participating sites, unplanned adjustment of the study design, and ultimately the loss of several potential sites. There were inconsistencies among RGOs minimum requirements and processes across jurisdictions and sites, with delays in obtaining approval signatures, time-consuming processes, differing platforms used to submit governance reviews and inflexibility of RGO processes all contributing to delays in progressing the trial and obtaining governance approval. The current governance process is time- and cost-consuming and undermines the NMA scheme's efforts to streamline the clinical trials review process.

Normal ranges of left atrial phasic strains and strain rates by 2D speckle-tracking echocardiography in pediatrics: a systematic review and meta-analysis

Establishing normal values of left atrial (LA) phasic strains and strain rates is essential for distinguishing between normal and abnormal functions, determining the degree of abnormality, and understanding the clinical significance of reported values in pediatrics. This meta-analysis aimed to establish normal values of two-dimensional speckle-tracking echocardiography (2DSTE)-derived LA phasic strains and strain rates in the pediatric population and identify the sources of inter-study heterogeneity for these values. A comprehensive search of PubMed, Scopus, and Embase databases was conducted using keywords such as “left atrial/left atrium,” “strain/speckle/deformation,” and “echocardiography” combined with pediatric age categories. Inclusion criteria comprised English-language human studies involving healthy subjects under 18 years of age. Subjects were categorized as neonates (up to 1 month), infants (1–12 months), and children (1–18 years). A random-effects model was applied to determine 2DSTE-derived LA strains and strain rates, and a meta-regression analysis was performed to investigate inter-study heterogeneity. Our analysis included 17 studies involving 1448 healthy subjects. For children, the mean values of LA strains during the reservoir, conduit, and contraction phases were 47.3% (95% CI 42.5–52.1%), 32.8% (95% CI 27.8–37.8%), and 12% (95% CI 10.0–14.1%), respectively. The mean values for LA strain rates were 2.4 s−1 (95% CI 1.1–3.8 s−1), 4.3 s−1 (95% CI 0.6–8.0 s−1), and 2.4 s−1 (95% CI 0.4–4.5 s−1), respectively. Inter-study heterogeneity for 2DSTE-derived LA phasic strains and strain rates was attributed to factors such as the number of study participants, publication year, software utilized, gating methods, the number of analyzed segments, the geographical region of the study, and heart rate. This study established the normal range of 2DSTE-derived LA phasic strains and strain rates. Additionally, inter-study heterogeneity was found to be influenced by various demographic, physiologic, and methodological factors.

Eicosanoids in coronary sinus negatively correlate with natriuretic peptides in heart failure with reduced ejection fraction: insights from Eicosanoids in Human Heart Failure Study

Abstract Background The diagnostic and therapeutic potential of eicosanoids, metabolites of arachidonic acid with positive cardio-renal activity in preclinical heart failure models, remains unclear in human chronic heart failure with reduced ejection fraction (HFrEF). Purpose The aim of this part of a traslational Eicosanoids in Human Heart Failure Study was to investigate levels of eicosanoids in different body compartments and their relation to natriuretic peptides. Methods Eleven consecutive patients with HFrEF indicated to cardiac resynchronisation therapy (CRT) were enrolled to measure plasmatic 14,15-epoxyeicosatrienoic acid (14,15-EET) and 14,15-dihydroxyicosatrienoic acid (14,15-DHET) levels from venous, arterial, and coronary sinus (CS) blood samples and correlate them with N-terminal pro B-type natriuretic peptide (NT-proBNP) from the same compartments. Results In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels (r = -0.63, p = 0.03) and positively with the DHET/EET ratio (r = 0.73, p = 0.02). This correlation was not found in the other compartments. Plasmatic 14,15-EET nor 14,15-DHET levels in measured compartments did not differ statistically (p = 0.21, p = 0,64, respectively). In individual patients, the levels of both eicosanoids correlated across all compartments. Peripheral plasma 14,15-EET levels in controls were lower compared to HF patients. Conclusion Peripheral venous eicosanoid (14,15-EET, 14,15-DHET) levels correlate and do not differ from arterial and CS levels in patients with HFrEF indicated to CRT. In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels and positively with the DHET/EET ratio, an indirect soluble epoxide hydrolase activity parameter.Graphical AbstractFigures

LCoRL regulates growth and metabolism.

Genome Wide Association Studies (GWAS) in humans and livestock have identified genes associated with metabolic traits. However, the causality of many of these genes on metabolic homeostasis is largely unclear due to lack of detailed functional analyses. Here we report Ligand Dependent Corepressor-Like (LCoRL) as a metabolic regulator for body weight and glucose homeostasis. Although GWAS data show that LCoRL is strongly associated with body size, glucose homeostasis, and other metabolic traits in humans and livestock, functional investigations had not been performed. We generated Lcorl knockout mice (Lcorl-/-) and characterized the metabolic traits. We found that Lcorl-/- pups are born smaller than the wildtype littermates (WT) before reaching normal weight by 7-9 weeks of age. While aging, Lcorl-/- mice remain lean compared to WT mice, which is associated with a decrease in daily food intake. Glucose tolerance and insulin sensitivity are improved in Lcorl-/- mice. Mechanistically, this stunted growth is linked to a reduction of circulating levels of insulin like growth factor-1. The expression of the genes downstream of growth hormone signaling and the genes involved in glucose and lipid metabolism are altered in the liver of Lcorl-/- mice. Furthermore, Lcorl-/- mice are protected against a high-fat diet (HFD) challenge and show reduced exercise capacity in an exercise stress test. Collectively, our results are congruent with many of the metabolic parameters linked to the Lcorl locus as reported in GWAS in humans and livestock.

GBNSS: A Method Based on Graph Neural Networks (GNNs) for Global Biological Network Similarity Search

Biological network similarity search plays a crucial role in the analysis of biological networks for human disease research and drug discovery. A biological network similarity search aims to efficiently identify novel networks biologically homologous to the query networks. Great progress has been achieved in biological network similarity searches. However, it remains a challenge to mine the biological network information fully to improve the accuracy of query results without increasing time overheads. In this study, we propose a biological network similarity search method based on graph neural networks named GBNSS, which combines topological and biological information (GO annotations) of biological networks into graph neural networks to find topologically and biologically similar biological networks in the database. Additionally, GBNSS is a topology-free biological network similarity search method with an arbitrary network structure. The experimental results on four benchmark datasets show that GBNSS outperforms the existing methods in terms of computational efficiency and search accuracy. Case studies further demonstrate that GBNSS is capable of searching similar networks in real-world biological networks.

Wine Phenolic Compounds: Chemistry, Functionality and Health Benefits

Wine phenolic compounds, often known as polyphenols, are a diverse group of secondary bioactive compounds derived from grapes. They play a crucial role in defining the sensory characteristics, functionality, and health benefits of wine. This review explores the complex chemistry of these compounds, focusing on key classes such as flavonoids, which include flavanones, flavonols, anthocyanins, and flavan-3-ols, and non-flavonoids, such as hydroxycinnamic acids, hydroxybenzoic acids, and stilbenes. The health benefits of wine phenolics, particularly their antioxidant and anti-inflammatory properties, are also discussed in relation to preventing and reducing the risk of non-communicable diseases (NCDs) such as cardiovascular diseases, cancers, and neurodegenerative conditions. Furthermore, this review summarized the most current data from human population-based research that investigated the bioactivity of these red wine phytochemicals with relevant health benefits for NCDs. Finally, this review proposes some perspectives for future research to better understand the bioavailability, metabolism, and long-term health effects of these compounds.

Air Pollutants and Ovarian Reserve: A Systematic Review of the Evidence

Abstract Background Growing evidence points to an association between ambient air pollution and decreased human reproductive potential. The aim of this study was to systematically review the association between air pollutants and female ovarian reserve. Methods The literature was searched in six electronic databases through August 2023. Screening of the 75 articles retrieved for inclusion criteria resulted in the selection of 12 human observational studies that evaluated the effect of environmental pollutants on markers of female ovarian reserve. The study protocol was registered on PROSPERO (registration code CRD42023474218). Results The study design of selected studies was found to be cross-sectional (2 of 10), retrospective cohort (7 of 10), prospective cohort (2 of 10), and case-control (1 of 10). The study population was equally distributed between Asians (60%) and Americans (50%) with an Italian minority (10%). The main findings showed a higher body of evidence for the environmental pollutants PM2.5, PM10, and NO2, while a low body of evidence for PM1, O3, SO2, and a very low body of evidence for benzene, formaldehyde, and benzo(a)pyrene, yet consistently showing significant inverse association data. The overall methodological quality of the selected studies was rated moderated across the 14 domains of the NIH toolkit. Conclusions Increased exposure to air pollutants seems to be associated with reduced female ovarian reserve with evidence being strongest for pollutants such as PM2.5, PM10, and NO2. More evidence is needed to draw conclusions about causality. Key messages • Increased exposure to air pollutants seems to be associated with reduced female ovarian reserve with evidence being strongest for pollutants such as PM2.5, PM10, and NO2. • Global environmental policy programs are urgently needed to reduce the risks associated with reduced fertility such as reduced birth rates or the use of assisted reproductive technologies.

MetaboScope: A statistical toolbox for analyzing 1H nuclear magnetic resonance spectra from human clinical studies

Abstract Motivation Metabolic phenotyping, using high-resolution spectroscopic molecular fingerprints of biological samples, has demonstrated diagnostic, prognostic, and mechanistic value in clinical studies. However, clinical translation is hindered by the lack of viable workflows and challenges in converting spectral data into usable information. Results MetaboScope is an analytical and statistical workflow for learning, designing and analyzing clinically relevant 1H nuclear magnetic resonance data. It features modular pre-processing pipelines, multivariate modeling tools including principal components analysis (PCA), orthogonal-projection to latent structure discriminant analysis, and biomarker discovery tools (multiblock PCA and statistical spectroscopy). A simulation tool is also provided, allowing users to create synthetic spectra for hypothesis testing and power calculations. Availability and implementation MetaboScope is built as a pipeline where each module accepts the output generated by the previous one. This provides flexibility and simplicity of use, while being straightforward to maintain. The system and its libraries were developed in JavaScript and run as a web app; therefore, all the operations are performed on the local computer, circumventing the need to upload data. The MetaboScope tool is available at https://www.cheminfo.org/flavor/metabolomics/index.html. The code is open-source and can be deployed locally if necessary. Module notes, video tutorials, and clinical spectral datasets are provided for modeling. Supplementary information Supplementary data are available at Bioinformatics Advances online.

Participation With Compensation: Ethical Considerations for Research Payment Practices With People Who Are Incarcerated.

The participation of incarcerated individuals in research is necessary to appropriately address the health disparities that affect them and to adapt and implement health services for the carceral setting. Incarceration significantly impacts health, leading to negative outcomes including accelerated aging and increased mortality, with these effects disproportionately impacting communities of color. The U.S. Department of Health and Human Services' Office for Human Research Protections outlines ethical approaches to compensating individuals who participate in research activities, yet lacks specific guidance for payment within carceral settings. Historical abuses in carceral research underscore the persistent need for robust protections for incarcerated research participants. Existing regulations offer some protection but inadequately address ethical payment practices. Substantial variability in payment policies across carceral systems and vague national guidelines pose ethical challenges in ensuring equitable treatment for incarcerated research participants. We outline the ethical concerns related to compensating incarcerated individuals for participating in research and present a framework of approaches to payment. We argue for payment parity between incarcerated and community research participants. More community-engaged research is needed to understand the perspectives of incarcerated individuals on ethical payment.

Two tiers, not one: Different sources of extrinsic mortality have opposing effects on life history traits.

Guided by concepts from life history (LH) theory, a large human research literature has tested the hypothesis that exposures to extrinsic mortality (EM) promote the development of faster LH strategies (e.g., earlier/faster reproduction, higher offspring number). A competing model proposes that, because EM in the past was intimately linked to energetic constraints, such exposures specifically led to the development of slower LH strategies. We empirically address this debate by examining (1) LH variation among small-scale societies under different environmental conditions; (2) country-, regional- and community-level correlations between ecological conditions, mortality, maturational timing, and fertility; (3) individual-level correlations between this same set of factors; and (4) natural experiments leveraging the impact of externally-caused changes in mortality on LH traits. Partially supporting each model, we found that harsh conditions encompassing energetic stress and ambient cues to EM (external cues received through sensory systems) have countervailing effects on the development of LH strategies, both delaying pubertal maturation and promoting an accelerated pace of reproduction and higher offspring number. We conclude that, although energetics are fundamental to many developmental processes, providing a first tier of environmental influence, this first tier alone cannot explain these countervailing effects. An important second tier of environmental influence is afforded by ambient cues to EM. We advance a 2-tiered model that delineates this second tier and its central role in regulating development of LH strategies. Consideration of the first and second tier together is necessary to account for the observed countervailing shifts toward both slower and faster LH traits.

Double-sided effect of selenium on blood lipids: A dose-response meta-analysis

Abstract Background Selenium, a trace element with both nutritional and toxicological properties, has been suggested to increase cardiovascular risk, particularly concerning diabetes and blood pressure levels. However, the impact of selenium exposure on the risk of dyslipidemia remains uncertain. This meta-analysis explored the shape of the relation between selenium exposure and its effects on lipid profiles in the most relevant experimental human studies, randomized controlled trials (RCTs). Materials and methods The review was registered in PROSPERO (ID: CRD42022380432). Through a bibliographic search conducted on PubMed, Web of Science, Embase, and the Cochrane Library, we identified RCTs investigating the impact of selenium supplementation on lipid profile. We then compared the results between intervention and control groups and, whenever possible, evaluated the non-linear relationship using a dose-response approach. Results We could include 26 RCTs involving different populations, i.e. healthy individuals, pregnant women, and subjects with health conditions such as cardiovascular diseases and Alzheimer’s dementia. Study endpoints were levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Our dose-response analysis indicated that selenium supplementation exceeding 200 µg/day adversely affected total cholesterol, HDL, and triglyceride levels. Hence, a threshold for such a detrimental effect of selenium was observed on total and HDL cholesterol and triglycerides, while opposite and inconsistent results emerged for levels below 200 µg/day and for LDL-cholesterol. Blood selenium levels at the end of the studies were positively associated with adverse effects on all endpoints. Conclusions This first dose-response meta-analysis of the effects of selenium on blood lipids highlights the potentially adverse effects of this trace element, in the amount and the chemical forms used in the trials. Key messages • Elevated selenium levels correlated with adverse effects on lipid profile. • Selenium doses exceeding 200 µg/day showed adverse effects on total and HDL cholesterol and triglycerides levels.

Peripheral blood immune cells distribution in biopsy-proven myocarditis: etiology and prognostic correlates

Abstract Background Myocarditis is an inflammatory disease of the myocardium with viral or immune-mediated/autoimmune etiology. Definite etiological diagnosis relays on endomyocardial biopsy (EMB). High titre anti-heart autoantibodies (AHA) define severe autoimmune forms. Virus-negative myocarditis may require immunosuppression (IS) to reduce progression to dilated cardiomyopathy, heart transplant or death. Prognostic stratification is incomplete and IS is not always efficacious. Animal and human studies suggest a pathogenetic role of immune cells, but little is known on their peripheral distribution or prognostic role. Purpose Characterize EMB-proven myocarditis patients’ peripheral blood to identify new non-invasive etiological and prognostic biomarkers. Methods Seventy-eight EMB-proven myocarditis patients and 9 healthy controls (HC) were enrolled according to the Declaration of Helsinki and written informed consent was collected for each participant. Peripheral blood mononuclear cells were purified by Ficoll stratification and immune cells distribution was evaluated by flow cytometry. Variables were analysed by Mann-Whitney or Kruskall-Wallis and Dunn post-hoc tests clustering patients according to clinical features, EMB and AHA results. Results Compared to HC (figure 1), plasmacytoid dendritic cells were reduced in myocarditis patients: with autoimmune/lymphocytic forms (p=0.0091); without extra cardiac autoimmune diseases (AD, p=0.0075); in those unresponsive to IS (p=0.0379) or never treated because of spontaneous healing (p=0.0015). Moreover, several immunophenotypical features discriminated myocarditis type/IS-response from HC. Viral forms were characterized by reduced CD94+ NK cells and CCR2 over-expression in intermediate monocytes (p=0.029, p=0.013). Autoimmune cases were defined by: higher CD62L+ NK cells when AHA negative (p=0.019); increased Th1 if not requiring IS (p=0.03); higher γδ-TCR+ Th17 and reduced Treg cells if without other AD (both p=0.04), or higher CD4+/IL17+ cells with concurrent AD (p=0.02) and AHA positivity (p=0.036). Moreover, ongoing IS treatment influenced peripheral cells distribution: whole blood cell counts were more frequently altered and total NK cells were reduced (p=0.007); treg cells were reduced in patients actively treated but unresponsive to IS (p=0.036). Conclusion Biopsy-proven myocarditis patients showed a skewed peripheral blood distribution of either innate or adaptive immune cells according to different histology, etiology (viral vs autoimmune) and response to IS in autoimmune forms, unveiling potential new non-invasive immunological biomarkers for myocarditis. Figure: Plasmacytoid dendritic cells (pDCs) percentage was assessed by flow-cytometry and data were showed by boxplots clustering myocarditis patients for etiology (A), EMB histological result (B), presence of extracardiac AD (C) or IS response (D). Data were analysed by Kruskall-Wallis (graph bottom) and Dunn post-hoc tests.

Factors that Influence Customer Loyalty in Online Banking Among University Students

Banks confronted tough competition in acquiring and maintaining consumers with their e-banking platforms due to the rising rate of use of e-banking systems. Essentially, improving e-banking service quality is seen as the best strategic strategy for increasing client loyalty to the e-banking system. The purpose of this paper was to empirically investigate a comprehensive mechanism for enhancing customer loyalty toward e-banking platforms via e-banking service. Reliability, website design, privacy and security, and customer service and support were the dimensions used. The objectives of this research included exploring relationships between factors such as customer satisfaction regarding online banking, reliability of service, quality and performance, service privacy and security in transactions, website design and its use, and the service and assistance in the usage, and customer loyalty. The respondents were among part 2 to part 5 students from Human Resources Studies in a higher learning institution. The researcher distributed the questionnaire to the respondents through the online method using social media accounts like WhatsApp, Instagram, and Telegram. The findings of the research included that, value and relevance were insights strategies to develop loyalty among student users. This included development and promotions with products like educational loan assistance, scholarship tracking tools, budget budget-friendly debit cards with student-specific features. Rewards, points, and other incentives should be used to make sure that online banking is being used frequently. Plugging the site along with its social features through a community forum made sure the students provided peer-to-peer support in sharing financial tips and experiences.