Predicting nanocarrier permeation across the human intestine : model matters.

For clinical translation of oral nanocarriers, simulation of the intestinal microenvironment during testing is crucial to evaluate interactions with the intestinal mucosa. However, studies are often conducted using simplistic cell culture models, overlooking key physiological factors, and potentially leading to an overestimation of nanocarrier permeation. In this study, we systematically investigate different tissue models of the human intestine under static cultivation and dynamic flow conditions and analyze the impact of altered tissue characteristics on nanocarrier permeation.

Effects of the glucagon-like peptide-1 receptor agonist dulaglutide on sexuality in healthy men: a randomised, double-blind, placebo-controlled crossover study.

Background: The reward-regulatory properties of GLP-1 are attracting increasing interest. Animal studies show that GLP-1 receptor agonists not only reduce consumption of addictive substances, but also influence sexual behaviour. We aimed to investigate the effect of dulaglutide versus placebo on sexual desire in humans.

TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1.

Viruses are able to efficiently penetrate cells, multiply, and eventually kill infected cells, release tumor antigens, and activate the immune system. Therefore, viruses are highly attractive novel agents for cancer therapy. Clinical trials with first generations of oncolytic viruses (OVs) are very promising but show significant need for optimization.

Effect of dulaglutide in promoting abstinence during smoking cessation: 12-month follow-up of a single-centre, randomised, double-blind, placebo-controlled, parallel group trial.

Background: Smoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the antidiabetic drug glucagon-like peptide-1 (GLP-1) analogue to modulate addictive behaviours and nicotine craving. Previously, we reported the short-term results of a randomised, double-blind, placebo-controlled trial.

Gender differences in weight gain during attempted and successful smoking cessation on dulaglutide treatment: a predefined secondary analysis of a randomised trial.

Background: Women seem to have more difficulty quitting smoking than men. This is particularly concerning as smoking puts women at a higher risk of developing smoking-associated diseases. Greater concerns about postcessation weight gain in women have been postulated as a possible explanation.

Effect of protein supplementation on plasma sodium levels in the syndrome of inappropriate antidiuresis: a monocentric, open-label, proof-of-concept study-the TREASURE study.

Importance: The syndrome of inappropriate antidiuresis (SIAD) can be treated with oral urea; however, compliance is impaired by its poor palatability.

Objective: To investigate whether dietary proteins could increase plasma sodium levels through urea-induced osmotic diuresis.

Design: An open-label, proof-of-concept trial.

Effect of dulaglutide in promoting abstinence during smoking cessation: a single-centre, randomized, double-blind, placebo-controlled, parallel group trial.

Background: Quitting smoking is difficult due to barriers such as craving for cigarettes and post-cessation weight gain. Recent experimental data suggest a role of glucagon-like peptide-1 (GLP-1) in the pathophysiology of addiction in addition to appetite regulation and weight control. We hypothesized that a pharmacological intervention with the GLP-1 analogue dulaglutide during smoking cessation may improve abstinence rates and reduce post-cessation weight gain.

PD-L1 Expression in Triple-negative Breast Cancer-a Comparative Study of 3 Different Antibodies.

Background: Assessment of programmed death protein-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has entered daily practice to identify patients eligible for treatment with immune checkpoint inhibitors. However, different antibodies and different cut-offs for PD-L1 positivity are used, and the interchangeability of these methods is not clear. The aim of our study was to analyze whether different PD-L1 antibodies can be used interchangeably to identify TNBC patients as PD-L1 positive.

Measuring the effectiveness of integrated vector management with targeted outdoor residual spraying and autodissemination devices on the incidence of dengue in urban Malaysia in the iDEM trial (intervention for Dengue Epidemiology in Malaysia): study protocol for a cluster randomized controlled trial.

Background: In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 h of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs.

Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing.

High attrition rates associated with drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies, our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia.

Targeted outdoor residual spraying, autodissemination devices and their combination against mosquitoes: field implementation in a Malaysian urban setting.

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia.

Connecting Cancer Pathways to Tumor Engines: A Stratification Tool for Colorectal Cancer Combining Human In Vitro Tissue Models with Boolean In Silico Models.

To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with -mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is-in contrast to melanoma-not effective in CRC, we combined it with the EGFR inhibitor gefitinib.

Efficacy of the OTSC System in the treatment of GI bleeding and wall defects: a PMCF meta-analysis.

Since its market launch in 2007, the endoscopic OTSC clipping system has been the object of intensive clinical research. These data were systematically collected for post-market clinical follow-up (PMCF). The aim of the study was the systematic review of the efficacy and safety of the OTSC System.

Properties Design: Prediction and Experimental Validation of the Luminescence Properties of a New Eu -Based Phosphor.

A theoretical model that allows to predict, for the first time, the luminescence properties of a new phosphor (BaSnSi O :Eu ) is presented. The predicted emission wavelength, 488 nm with a 64 nm bandwidth, was confirmed by subsequent experimental work. The method consists in a multi-electron Hamiltonian parametrized from ab initio calculations.

Photoluminescence and energy transfer behavior of narrow band red light emitting LiBaTb(MoO):Eu.

This work concerns the polycrystalline red emitting solid state compound LiBa(TbEu)(MoO), from which a series of powder samples was prepared by a conventional solid-state reaction. The phase formation of the samples was investigated by X-ray diffraction which revealed the formation of a solid solution without a miscibility gap. Photoluminescence (PL) spectra and decay curves were recorded as a function of Tb and Eu concentration and temperature.

Mimicking Metastases Including Tumor Stroma: A New Technique to Generate a Three-Dimensional Colorectal Cancer Model Based on a Biological Decellularized Intestinal Scaffold.

Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc).

Endoscopic full-thickness resection and clip defect closure in the colon with the new FTRD system: experimental study.

Background: The benefit of endoscopic full-thickness resection is the improved diagnostic work-up with an integral wall specimen which allows a precise determination of the tumor or its precursor and its infiltration depth into the wall.

Materials And Methods: A new endoscopic full-thickness resection device (FTRD), which is a combination of a modified over-the-scope-clip (OTSC) system with an electrocautery snare, has been tested in an experimental setting. In eleven pigs, divided into three groups, endoscopic full-thickness resection was performed in the colon at one or two sites, respectively.

Endoluminal full-thickness resection of GI lesions: a new device and technique.

Full-thickness resection techniques are of growing interest in the field of endoscopic removal of tumors or their precursors in the digestive tract. A new dedicated full-thickness resection device has been developed based on the combination of the OTSC clip, an enlarged resection cap and an integrated snare. The device prototype allows combined resection of all gastrointestinal organ wall layers in one maneuver, up to a size of 3 x 3 cm.

Development and implementation of a technical and didactical training program for student tutors in the dissection course.

Background: student tutors have a long tradition in gross anatomy instruction. However, the full potential of the tutors is generally not tapped, since little attention is paid to their technical and didactical training. The aim of this paper is to report a systematic approach to the development, didactic reasoning and implementation of a curriculum for training student tutors in gross anatomy.

The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist.

Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds.

A new serrated snare for improved tissue capture during endoscopic snare resection.

Endoscopic snare resection of gastrointestinal polyps and neoplasm is a standard procedure in interventional endoscopy. Due to technical and procedural improvements the removal of large sessile polyps can be achieved by endoscopic mucosal resection either in one single specimen or by piecemeal resection. In this experimental study a new snare with special teeth attached to the distal part of the wire loop was evaluated and compared to a conventional snare.

Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts.

Background: The zinc finger protein Sp2 (specificity protein 2) is a member of the glutamine-rich Sp family of transcription factors. Despite its close similarity to Sp1, Sp3 and Sp4, Sp2 does not bind to DNA or activate transcription when expressed in mammalian cell lines. The expression pattern and the biological relevance of Sp2 in the mouse are unknown.

Role of sphingosine-1-phosphate (S1P) and the S1P(2) receptor in allergen-induced, mast cell-dependent contraction of rat lung parenchymal strips.

Lung parenchymal strips isolated from ovalbumin-sensitized rats manifest a mast cell-dependent, biphasic contraction when challenged with allergen. The first phase is mediated by the release of preformed 5-HT while the second phase is dependent on de novo synthesis of leukotrienes. Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite which is readily generated in mast cells and has been demonstrated to be an important regulator of allergen-induced mast cell activation.