Integrated Screening Approach Research Articles

Accuracy, Acceptability, and Burden of an Integrated Screening Approach to Facilitate the Delivery of Tailored Sexual Assault Prevention in the U.S. Air Force

ABSTRACT This paper examines accuracy, acceptability, and respondent burden of integrated screening to facilitate tailored sexual assault (SA) prevention program delivery in a basic military training (BMT) environment. Trainees (n = 5,951) received tailored prevention content based on self-reported sex, sexual orientation, prior SA victimization and perpetration, and past-month post-traumatic stress symptoms. Bivariate analyses examined trainee-reported screener accuracy, acceptability, and burden, including differences by tailoring-targeted subgroups (e.g. men/women). Overall accuracy and acceptability were high (>90%) despite significant subgroup variability. Screening time averaged 10.55 (SD = 1.95) minutes; individuals with prior SA took longer. Missingness increased linearly throughout the screener. Integrated screening is an accurate, acceptable way to deploy tailored SA prevention in BMT. Findings inform data-driven screening improvements and novel applications.

Screening for hepatitis C virus at the time of mammography using rapid diagnostic tests in women aged between 50 and 74 years (Mamm'OC NCT05067374).

Chronic hepatitis C Virus (HCV) infection presents a global health challenge, with significant morbidity and mortality worldwide. Despite remarkable progress in treatment options, achieving elimination targets by 2030, as set by the World Health Organization, remains elusive. Our study aimed to address this gap by integrating HCV screening into a national breast cancer screening program. Between March 2022 and March 2023, a prospective cross-sectional multicenter study was conducted in four radiology centers in Montpellier, France. We proposed HCV screening to consecutive women undergoing mammography, targeting 1,500 participants aged 50-74 years. A rapid diagnostic test (RDT) for HCV antibodies (HCV Ab) was performed on capillary whole blood, with positive cases undergoing serological and RNA confirmation. Participants also completed a questionnaire on demographic data and risk factors. Acceptance rates, HCV prevalence, and linkage to care were assessed. The acceptance rate for this integrated screening approach was 82.4%. Notably, the seroprevalence of HCV was found to be 0.65%. Linkage to care was prompt, and the cascade of care demonstrated successful treatment outcomes. Importantly, the majority of detected infections were successfully resolved. These findings underscore the feasibility and acceptability of integrating HCV screening with breast cancer screening programs providing updated prevalence data and valuable insights for refining future screening strategies.

Cardiotoxicity Assessment through a Polymer-Based Cantilever Platform: An Integrated Electro-Mechanical Screening Approach.

Preclinical drug screening for cardiac toxicity has traditionally relied on observing changes in cardiomyocytes' electrical activity, primarily through invasive patch clamp techniques or non-invasive microelectrode arrays (MEA). However, relying solely on field potential duration (FPD) measurements for electrophysiological assessment can miss the full spectrum of drug-induced toxicity, as different drugs affect cardiomyocytes through various mechanisms. A more comprehensive approach, combining field potential and contractility measurements, is essential for accurate toxicity profiling, particularly for drugs targeting contractile proteins without affecting electrophysiology. However, previously proposed platform has significant limitations in terms of simultaneous measurement. The novel platform addresses these issues, offering enhanced, non-invasive evaluation of drug-induced cardiotoxicity. It features eight cantilevers with patterned strain sensors and MEA, enabling real-time monitoring of both cardiomyocyte contraction force and field potential. This system can detect minimum cardiac contraction force of ≈2 µN and field potential signals with 50µm MEA diameter, using the same cardiomyocytes in measurements of two parameters. Testing with six drugs of varied mechanisms of action, the platform successfully identifies these mechanisms and accurately assesses toxicity profiles, including drugs not inhibiting potassium channels. This innovative approach presents a comprehensive, non-invasive method for cardiac function assessment, poised to revolutionize preclinical cardiotoxicity screening.

Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1.

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased NF-κB-dependent apoptosis specifically in tumors and not normal tissues, indicating that, in malignant cells, C5aR1 primarily regulated cell fate. Collectively, these data revealed that increased complement gene expression is part of the stress response mounted by irradiated tumors and that targeting C5aR1 could improve radiotherapy, even in tumors displaying immunosuppressive features.

Integrated immune monitoring of HCMV infection in pregnant women with complications and its association with adverse pregnancy outcomes

Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant women (n = 67) with complications including BOH and associated these signatures with pregnancy outcomes. Infection status was determined using nested blood PCR, seropositivity and IgG avidity by ELISA. Systemic and HCMV specific (pp65) cellular immune responses were evaluated by flow cytometry. Seropositivity was determined for other TORCH pathogens (n = 33) on samples with recorded pregnancy outcomes. This approach was more sensitive in detecting HCMV infection. Blood PCR positive participants, irrespective of their IgG avidity status, had higher cytotoxic potential in circulating CD8+ T cells (p < 0.05) suggesting that infection associated cellular dysfunction was uncoupled with avidity maturation of antiviral humoral responses. Also, impaired anamnestic degranulation of HCMV-pp65-specific T cells compared to HCMV blood PCR negative participants (p < 0.05) was observed. APO correlated with HCMV blood PCR positivity but not serostatus (p = 0.0039). Most HCMV IgM positive participants (5/6) were HCMV blood PCR positive with APO. None were found to be IgM positive for other TORCH pathogens. Multiple TORCH seropositivity however was significantly enriched in the APO group (p = 0.024). Generation of HCMV specific high avidity IgG antibodies had no bearing on APO (p = 0.9999). Our study highlights the utility of an integrated screening approach for antenatal HCMV infection in the context of BOH, where infection is associated with systemic and virus specific cellular immune dysfunction as well as APO.

The market uncertainty of ethically compliant equity: An integrated screening approach

This study investigates the uncertainty of market returns for ethically compliant equity using a comprehensive ethical screening methodology. The analysis also compares the effect of different ethical screening criteria on firm uncertainty. We develop a comprehensive ethical screening framework that fulfils the intrinsic value of the Islamic religion and responds to contemporary ethical challenges. Using the comprehensive framework, a global sample of non-financial companies are screened for their fulfilment of religious and ethical values. The framework is not only focused on basic screening methodologies that are currently used in the Islamic finance industry but also covers the aspect of environmental, social and governance (ESG) performance, as well as firms’ earnings qualities. The analysis reveals that ethically compliant firms display lower uncertainty than non-ethically compliant firms. The level of firm uncertainty is also different between the screening stages, where firms screened using a more comprehensive ethical approach are exposed to lower uncertainty. The results are robust to various estimations and consistent during the 2008 financial crisis.

Barriers and Facilitators to Participation in Health Screening: an Umbrella Review Across Conditions.

Screening is an essential prevention practice for a number of health conditions. However, screening coverage remains generally low. Studies that investigate determinants of screening participation are becoming more common, but oftentimes investigate screening for health conditions in an individualized rather than integrated fashion. In routine clinical practice, however, healthcare professionals are often confronted with situations in which several screening procedures are recommended for the same patient. The consideration of their common determinants may support a more integrated screening approach. The objectives of this umbrella review were therefore to examine: 1) the determinants (barriers and facilitators) that have been identified in relation to recommended health screening procedures; and 2) the modifiable determinants (in primary care) common across health conditions or specific to individual procedures. Results were presented through a narrative synthesis. PubMed, PsycInfo and Cochrane weresearched up to January 2022. Systematic reviews reporting determinants of participation in health screening procedures with grade A or B recommendation according to the US Preventive Services Task Forcewere included. A total of 85 systematic reviews were included, most which contained both qualitative and quantitative studies on determinants that describe individual factors (961 occurrences), social factors (113 occurrences, healthcare professional factors (149 occurrences), health system factors (105 occurrences) and screening procedure factors (99 occurrences). The most studied screening procedures concerned cervical cancer/human papillomavirus (n = 33), breast cancer (n = 28), colorectal cancer (n = 25) and the human immunodeficiency virus (n = 12). Other conditions have been under-studied (e.g. cardiovascular problems, lung cancer, syphilis). The individual domain, including determinants such as knowledge, beliefs and emotions, was the most covered across health conditions. Healthcare professional's recommendations and the quality of patient-provider communication were identified to have a strong influence on screening participation in most conditions. The other three domains included determinants which were more specific to a condition or a population. Various determinants modifiable in primary care were found in the individual domain and in the health system, healthcare professional and screening procedure domains. Quality was assessed as low for most systematic reviews included. The identification of various modifiable determinants common across conditions highlights the potential of an integrated screening participation approach. Interventions may address common determinants in a broader person-centred framework within which tailoring to specific procedures or populations can be considered. This approach needs to be explored in intervention studies. The systematic review registration is PROSPERO CRD42019126709.

A new perspective to improve the treatment of Lianhuaqingwen on COVID-19 and prevent the environmental health risk of medication.

Lianhuaqingwen (LH), one traditional Chinese medicine (TCM), has been used to treat the coronavirus disease 2019 (COVID-19), but its ecotoxicity with potential human health security has not been well investigated. To overcome such adverse effects and improve its medication efficacy, an intelligent multi-method integrated dietary scheme, screening, and performance evaluation approach was developed. Thirteen LH compounds were selected, and the main protease (Mpro) was used as the potential drug target. Resulted information showed that the more compounds of LH added, the higher medication efficacy obtained using multi-method integrated screening system, expert consultation method, and molecular dynamics simulation. Pharmacodynamic mechanism analysis showed that low total energy and polar surface area of LH active compound (i.e., β-sitosterol) will contribute to the best therapeutic effect on COVID-19 using quantitative structure-activity relationships (QSAR) and sensitivity models. Additionally, when mild COVID-19 patients take LH with the optimum dietary scheme (i.e., β-lactoglobulin, α-lactalbumin, vitamin A, vitamin B, vitamin C, carotene, and vitamin E), the medication efficacy were significantly improved (23.58%). Pharmacokinetics and toxicokinetics results showed that LH had certain human health risks and ecotoxicity. This study revealed the multi-compound interaction mechanism of LH treatment on COVID-19, and provided theoretical guidance for improving therapeutic effect, evaluating TCM safety, and preventing human health risk.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-022-21125-w.

Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.

INTRODUCTION:Mounting evidence demonstrates potential for fecal–oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens.METHODS:A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients.RESULTS:The dual-target and single-target limit of detection were 56 copies/μL and 3 copies/μL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/μL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001).DISCUSSION:The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.

A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking.

Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5p more potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. SIGNIFICANCE: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.

Metoprolol and metoprolol acid degradation in UV/H2O2 treated wastewaters: An integrated screening approach for the identification of hazardous transformation products.

Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study describes the development of an integrated screening approach to determine the highest number of pharmaceutical transformation products (TPs) in a single run. The identification of TPs was based on the comparison of detected features with literature sources, compound prediction tools, in-house libraries and reference standards using high-resolution mass spectrometry (HRMS). This integrated approach allowed a better estimation (in silico) of the ecotoxicological contribution of the individual TPs identified. As a proof of concept, this methodology was applied for identification of the TPs generated from metoprolol and its main human metabolite (metoprolol acid) in pure water, hospital wastewater and industrial wastewater treated by UV/H2O2. Twenty-four TPs with potential ecotoxicological implications were identified and their presence was pinpointed as a function of the treated wastewater. An integrated screening approach has been developed using four different screening methodologies in the same run. Additionally, the metabolite MTPA has been considered as a target pollutant in UV/H2O2 experiments.

Lipids in benthic diatoms: A new suitable screening procedure

The selection of suitable and indigenous microalgae species is a fundamental requirement in developing added-value bioactive compounds recoverable in the food, health, and cosmetics markets. In this work, an integrated screening approach was developed to characterize the lipid rate of 33 diatom species (including 15 species studied for the first time) belonging to 16 genera from the Nantes Culture Collection, with the main objective of discovering bioactive lipid producers. For that purpose, a simple reliable method for establishing growth kinetics of strains and semi-quantitative analysis of lipid rates was developed. Growth kinetics measurements were achieved by daily minimal measurement fluorescence (F0) whereas lipid rate analyses were performed by high-throughput Fourier Transform Infrared spectroscopy on entire cells and lipid extracts. Results indicated that the method could be used directly on entire cells in spite of the presence of silica for the FTIR approach (due to frustule). The total lipid rate was species-dependant and ranged from 3.7% to 30.5% DW. Six strains out of 33 were found to present a higher total lipid rate superior to 15% DW, and 11 showed medium lipid rates ranging from 10% to 15% DW. The results revealed that five diatom species i.e. Amphora sp. NCC169, Nitzschia sp. NCC109, Nitzschia alexandrina NCC33, Opephora sp. NCC366 and Staurosira sp. NCC182 presented interesting growth capabilities and should be further investigated as potential sources for their original lipid rate.

Gene expression profiles and signaling mechanisms in \u03b12B-adrenoceptor-evoked proliferation of vascular smooth muscle cells

Backgroundα2-adrenoceptors are important regulators of vascular tone and blood pressure. Regulation of cell proliferation is a less well investigated consequence of α2-adrenoceptor activation. We have previously shown that α2B-adrenoceptor activation stimulates proliferation of vascular smooth muscle cells (VSMCs). This may be important for blood vessel development and plasticity and for the pathology and therapeutics of cardiovascular disorders. The underlying cellular mechanisms have remained mostly unknown. This study explored pathways of regulation of gene expression and intracellular signaling related to α2B-adrenoceptor-evoked VSMC proliferation.ResultsThe cellular mechanisms and signaling pathways of α2B-adrenoceptor-evoked proliferation of VSMCs are complex and include redundancy. Functional enrichment analysis and pathway analysis identified differentially expressed genes associated with α2B-adrenoceptor-regulated VSMC proliferation. They included the upregulated genes Egr1, F3, Ptgs2 and Serpine1 and the downregulated genes Cx3cl1, Cav1, Rhoa, Nppb and Prrx1. The most highly upregulated gene, Lypd8, represents a novel finding in the VSMC context. Inhibitor library screening and kinase activity profiling were applied to identify kinases in the involved signaling pathways. Putative upstream kinases identified by two different screens included PKC, Raf-1, Src, the MAP kinases p38 and JNK and the receptor tyrosine kinases EGFR and HGF/HGFR. As a novel finding, the Src family kinase Lyn was also identified as a putative upstream kinase.Conclusionsα2B-adrenoceptors may mediate their pro-proliferative effects in VSMCs by promoting the activity of bFGF and PDGF and the growth factor receptors EGFR, HGFR and VEGFR-1/2. The Src family kinase Lyn was also identified as a putative upstream kinase. Lyn is known to be expressed in VSMCs and has been identified as an important regulator of GPCR trafficking and GPCR effects on cell proliferation. Identified Ser/Thr kinases included several PKC isoforms and the β-adrenoceptor kinases 1 and 2. Cross-talk between the signaling mechanisms involved in α2B-adrenoceptor-evoked VSMC proliferation thus appears to involve PKC activation, subsequent changes in gene expression, transactivation of EGFR, and modulation of kinase activities and growth factor-mediated signaling. While many of the identified individual signals were relatively small in terms of effect size, many of them were validated by combining pathway analysis and our integrated screening approach.

P144 Optimising chlamydia screening – a city and countywide approach in nottinghamshire

IntroductionThe Public Health Outcomes Framework detection rate indicator (DRI) sets a target of ≥2,300 chlamydia diagnoses per 100,000 15 to 24 year-olds. The 2014 DRI in Nottingham City and Nottinghamshire County was 2,807 and 1,900, respectively.We used the National Chlamydia Screening Programme’s Chlamydia Care Pathway (CCP) approach to review 2014 data and identify opportunities to improve the quality of screening and increase the DRI.MethodsRoutine surveillance data from GUMCAD and CTAD was used to populate the CCP for the region. Findings were discussed at the local strategic sexual health group and actions agreed.ResultsIssues identified were around unknown test offer-rate, low coverage in some districts and low retesting rates following treatment. In response: existing GUMCAD codes were used to infer the offer of a test; health promotion activities focused on raising awareness of testing among key populations, primary care and providers of other young person services; re-testing pathways were audited and a text reminder system for re-screening at 3months was implemented in one of the units.DiscussionThe CCP provided a strategic focus to increase understanding of screening at all stages of the pathway. It confirmed the need for an integrated screening approach across sexual health providers, primary care and broader health services who engage with young people. There was potential to achieve ‘quick wins’ by using the CCP to focus on each specific stage of the programme. 2017 data will be reviewed using the CCP to evaluate the impact of the plans which have been implemented.

Multi-functional activities of citrus flavonoid narirutin in Alzheimer’s disease therapeutics: An integrated screening approach and in vitro validation

Alzheimer’s disease (AD) is a complex disorder and the disease mechanism is yet to be properly characterized. Over the years, “amyloid cascade” emerges as principal pathogenic event in AD. β-Secretase 1 (BACE1) controls the rate-limiting step in amyloid beta (Aβ) generation and Aβ rapidly aggregates to form neurotoxic amyloid fibrils. Oxidative stress is one of the principal mediators of the observed neurotoxicity of amyloid fibril. The disease pathogenesis involves induction of multiple signaling cascades and the cross-talk therein. Thus inhibiting multiple targets could be an attractive therapeutic strategy. Here, a multi-target virtual screening protocol has been devised and used to screen an in house developed phytochemical library. Narirutin comes out as a multi-potent phytochemical. Steady-state and time-resolved fluorescence along with molecular modelling studies demonstrate its binding to the BACE1 active site that induces a conformational transition of the protein from open to closed form which precludes substrate recognition. Narirutin possesses strong Aβ aggregation inhibitory potential, evident from ANS and Thioflavin-T binding assay and confirmed by AFM study. ABTS·+ scavenging assay shows moderate antioxidant activity for narirutin. The applicability of a multi-target screening strategy in AD therapeutics is thus demonstrated and the identified hit, narirutin, shows strong multi-potent activity.

Editor's Highlight: Screening ToxCast Prioritized Chemicals for PPARG Function in a Human Adipose-Derived Stem Cell Model of Adipogenesis.

The developmental origins of obesity hypothesis posits a multifaceted contribution of factors to the fetal origins of obesity and metabolic disease. Adipocyte hyperplasia in gestation and early childhood may result in predisposition for obesity later in life. Rodent in vitro and in vivo studies indicate that some chemicals may directly affect adipose progenitor cell differentiation, but the human relevance of these findings is unclear. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARG) is the master regulator of adipogenesis. Human adipose-derived stem cells (hASC) isolated from adipose tissue express endogenous isoforms of PPARG and represent a biologically relevant cell-type for evaluating activity of PPARG ligands. Here, a multi-endpoint approach based on a phenotypic adipogenesis assay was applied to screen a set of 60 chemical compounds identified in ToxCast Phase I as PPARG active (49) or inactive (11). Chemicals showing activity in the adipogenesis screen were further evaluated in a series of 4 orthogonal assays representing 7 different key events in PPARG-dependent adipogenesis, including gene transcription, protein expression, and adipokine secretion. An siRNA screen was also used to evaluate PPARG-dependence of the adipogenesis phenotype. A universal concentration-response design enabled inter-assay comparability and implementation of a weight-of-evidence approach for bioactivity classification. Collectively, a total of 14/49 (29%) prioritized chemicals were identified with moderate-to-strong activity for human adipogenesis. These results provide the first integrated screening approach of prioritized ToxCast chemicals in a human stem cell model of adipogenesis and provide insight into the capacity of PPARG-activating chemicals to modulate early life programming of adipose tissue.

Macro and micro models for zonal crash prediction with application in hot zones identification

Zonal crash prediction has been one of the most prevalent topics in recent traffic safety research. Typically, zonal safety level is evaluated by relating aggregated crash statistics at a certain spatial scale to various macroscopic factors. Another potential solution is from the micro level perspective, in which zonal crash frequency is estimated by summing up the expected crashes of all the road entities located within the zones of interest. This study intended to compare these two types of zonal crash prediction models. The macro-level Bayesian spatial model with conditional autoregressive prior and the micro-level Bayesian spatial joint model were developed and empirically evaluated, respectively. An integrated hot zone identification approach was then proposed to exploit the merits of separate macro and micro screening results. The research was based on a three-year dataset of an urban road network in Hillsborough County, Florida, U.S.Results revealed that the micro-level model has better overall fit and predictive performance, provides better insights about the micro factors that closely contribute to crash occurrence, and leads to more direct countermeasures. Whereas the macro-level crash analysis has the advantage of requirement of less detailed data, providing additional instructions for non-traffic engineering issues, as well as serving as an indispensable tool in incorporating safety considerations into long term transportation planning. Based on the proposed integrated screening approach, specific treatment strategies could be proposed to different screening categories. The present study is expected to provide an explicit template towards the application of either technique appropriately.

Development of a screening procedure for the characterization of Botryococcus braunii strains for biofuel application

An integrated screening approach was developed to assess the potential of the Botryococcus genus for the production of lipids for biofuel application (hydrocarbons and triacylglycerols). The strategy developed in this study permitted to rigorously measure mandatory parameters for the determination of strain performance – i.e. growth rate and oil content. For that purpose, mini-photobioreactors run in parallel were used together with an exhaustive lipid class analysis. The quantitative productivity measurements indicated that the ten screened strains presented very different patterns in the conditions of PBR culture, firstly run in batch, and secondly in continuous mode. Indeed, with the applied setup, only four strains presented biomass productivities close to that previously measured for the reference strain 807/1 (between 74 and 307mgL−1day−1 of biomass for the tested strains). HC productivity obtained under continuous light (∼14mgL−1day−1) was close to that measured for the strain 807/1 (∼20mgL−1day−1), confirming B. braunii tested strains potential for biofuel application. The analysis of the lipid chemodiversity revealed moreover that this genus should be further investigated for its polar lipids, as it suggests potential pharmaceutical applications such as production of antitumorals or immunosuppressors.

Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs

Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs

Simultaneous and dose dependent melanoma cytotoxic and immune stimulatory activity of betulin.

Conventional cytostatic cancer treatments rarely result in the complete eradication of tumor cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established tumors. In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of tumor tissue. Genistein, fingolimod and betulin have already been described as active compounds in different types of cancer. Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different B16 melanoma cell lines to a given extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while genistein and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in comparison to the melanoma cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measured by the IL-12p70 release of Toll-like receptor 4-stimulated BMDCs by ELISA, which was due to increased IL-12p35 mRNA expression. Interestingly, the activation of DCs resulted in enhanced T lymphocyte stimulation, indicated by increased IL-2 and IFN-γ production of cytotoxic T cells in spleen cell co-culture assays which led to a decreased viability of B16 cells in an antigen specific model system. This may overcome the immunosuppressive environment of a tumor and destroy tumor cells more effectively in vivo if the immune response is specific targeted against the tumor tissue by antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin, that simultaneously exhibit immune stimulatory activity may serve as lead compounds and hold great promise as a novel approach for an integrated cancer therapy.