Biomagnetic methodologies for the noninvasive investigations of the human brain (Magnobrain)

Magnetoencephalography (MEG) non-invasively infers the distribution of electric currents in the brain by measuring the magnetic fields they induce. Its superb spatial and temporal resolution provides a solid basis for the `functional imaging¿ of the brain provided it is integrated with other brain imaging techniques. MAGNOBRAIN is an applied research project that developed tools to integrate MEG with MRI and EEG. These include: (1) software for MEG oriented MRI feature extraction; (2) the Brain Data Base (BDB) which is a reference library of information on the brain used for more realistic and biologically meaningful functional localisations through MEG and EEG; and (3) a database of normative data (age and sex matched) for the interpretation of MEG. It is expected that these tools will evolve into a medical informatics environment that will aid the planning of neurosurgical operations as well as contribute to the exploration of mental function including the study of perception and cognition

Confocal Laser Endomicroscopy for Diagnosis of Barrett’s Esophagus

Barrett’s esophagus (BE) is established as a premalignant condition in the distal esophagus. Current surveillance guidelines recommend random biopsies every 1–2 cm at intervals of 3–5 years. Advanced endoscopic imaging of BE underwent several technical revolutions within the last decade including broad-field (red-flag) techniques (e.g., chromoendoscopy) and small-field techniques with confocal laser endomicroscopy (CLE) at the forefront. In this review we will focus on advanced endoscopic imaging using CLE for the diagnosis and characterization of BE and associated neoplasia. In addition, we will critically discuss the technique of CLE and provide some tricks and hints for the daily routine practice of CLE for diagnosis of BE

Splicing factor ESRP1 controls ER-positive breast cancer by altering metabolic pathways

The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels of ESRP1, but not ESRP2, are associated with poor prognosis in estrogen receptor positive (ER+) breast tumors. Knockdown of ESRP1 in endocrine-resistant breast cancer models decreases growth significantly and alters the EMT splicing signature, which we confirm using TCGA SpliceSeq data of ER+ BRCA tumors. However, these changes are not accompanied by the development of a mesenchymal phenotype or a change in key EMT-transcription factors. In tamoxifen-resistant cells, knockdown of ESRP1 affects lipid metabolism and oxidoreductase processes, resulting in the decreased expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH) at both the mRNA and protein levels. Furthermore, ESRP1 knockdown increases the basal respiration and spare respiration capacity. This study reports a novel role for ESRP1 that could form the basis for the prevention of tamoxifen resistance in ER+ breast cancer

Semantic segmentation of non-linear multimodal images for disease grading of inflammatory bowel disease: A segnet-based application

Non-linear multimodal imaging, the combination of coherent anti-stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), has shown its potential to assist the diagnosis of different inflammatory bowel diseases (IBDs). This label-free imaging technique can support the ‘gold-standard’ techniques such as colonoscopy and histopathology to ensure an IBD diagnosis in clinical environment. Moreover, non-linear multimodal imaging can measure biomolecular changes in different tissue regions such as crypt and mucosa region, which serve as a predictive marker for IBD severity. To achieve a real-time assessment of IBD severity, an automatic segmentation of the crypt and mucosa regions is needed. In this paper, we semantically segment the crypt and mucosa region using a deep neural network. We utilized the SegNet architecture (Badrinarayanan et al., 2015) and compared its results with a classical machine learning approach. Our trained SegNet mod el achieved an overall F1 score of 0.75. This model outperformed the classical machine learning approach for the segmentation of the crypt and mucosa region in our study

Computational tissue staining of non-linear multimodal imaging using supervised and unsupervised deep learning

Hematoxylin and Eosin (H&E) staining is the 'gold-standard' method in histopathology. However, standard H&E staining of high-quality tissue sections requires long sample preparation times including sample embedding, which restricts its application for 'real-time' disease diagnosis. Due to this reason, a label-free alternative technique like non-linear multimodal (NLM) imaging, which is the combination of three non-linear optical modalities including coherent anti-Stokes Raman scattering, two-photon excitation fluorescence and second-harmonic generation, is proposed in this work. To correlate the information of the NLM images with H&E images, this work proposes computational staining of NLM images using deep learning models in a supervised and an unsupervised approach. In the supervised and the unsupervised approach, conditional generative adversarial networks (CGANs) and cycle conditional generative adversarial networks (cycle CGANs) are used, respectively. Both CGAN and cycle CGAN models generate pseudo H&E images, which are quantitatively analyzed based on mean squared error, structure similarity index and color shading similarity index. The mean of the three metrics calculated for the computationally generated H&E images indicate significant performance. Thus, utilizing CGAN and cycle CGAN models for computational staining is beneficial for diagnostic applications without performing a laboratory-based staining procedure. To the author's best knowledge, it is the first time that NLM images are computationally stained to H&E images using GANs in an unsupervised manner

Esophageal Epithelial Resistance

Besides its important role of digestion and absorption, esophageal tissue has an essential role as a major barrier against intraluminal pathogens like hostile microorganisms and toxins. This barrier function is achieved via various mechanical, chemical, and immunological mechanisms which are typically altered in inflammatory diseases, thereby causing subsequent damage of the mucosa. In this review we will focus on the main structural and functional barriers of host defense within the esophageal mucosa, including the epithelial layer, membrane-bound and secretory mucins, and different types of defensins. In addition, we will discuss the relevance of biofilm on esophageal tissue and will illustrate the importance of different regulators of intestinal permeability like zonulin and desmosomal components

Advanced Endoscopic Imaging for Diagnosis of Crohn's Disease

Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to evaluate therapeutic success and for the surveillance of colitis associated cancer. Thus it becomes obvious that there is a need for new and more advanced endoscopic imaging techniques for better characterization of mucosal inflammation and early neoplasia detection in IBD. This paper describes the concept of advanced endoscopic imaging for the diagnosis and characterization of Crohn's disease, including magnification endoscopy, chromoendoscopy, balloon-assisted enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy

Management of an extended clivus fracture: a case report

Background: Clivus fractures are highly uncommon. The classification by Corradino et al. divides the different lesions in longitudinal, transverse and oblique fractures. Longitudinal types are associated with the highest mortality rate between 67 – 80%. Clivus fractures are often found after high velocity trauma, especially traffic accidents and falls. The risk of neurologic lesions is high, because of the anatomic proximity to neurovascular structures like the brainstem, the vertebrobasilar artery, and the cranial nerves. Longitudinal clivus fractures have a special risk of causing entrapment of the basilar artery and thus ischemia of the brainstem. Case presentation: This lesion in our patient was a combination-fracture of the craniocervical junction with a transverse clivus fracture. In this case, the primary closed reduction of the clivus fracture and the immobilization with a halo device was the therapy of choice and led to consolidation of the fracture. Conclusion: Therapy advices and examples in the literature are scarce. We present a patient with a clivus fracture, who could be well treated by a halo device. Through detailed research of the literature a therapy algorithm has been developed.<br

Rapid Detection of Quinolone Resistance Mutations in gyrA of Helicobacter pylori by Real-Time PCR

The treatment of infections by the gastric pathogen Helicobacter pylori (H. pylori) has become more difficult due to increased rates of resistances against various antibiotics. Typically, atriple therapy, employing a combination of at least two antibiotics and a proton pump inhibitor, is used to cure H. pylori infections. In case of first-line therapy failure, quinolones are commonly applied in a second-line therapy. To prevent second-line treatment failures, we developed an improved method to detect the most common quinolone-resistance mutations located in the quinolone-resistance-determining region (QRDR) of the bacterial gyrA gene. Biopsy material from the gastric mucosa of infected patients was used to identify quinolone-resistant strains before the onset of drug administration. Two different wild-type and six mutant QRDR sequences were included. Melting curve analyses were performed with corresponding gyrA plasmid DNAs using a real-time polymerase chain reaction (RT-PCR) assay. By applying a combination of only two different fluorescent probes, this assay allows wild-type sequences to be unambiguously distinguished from all known mutant QRDR sequences of H. pylori. Next, the T(m) values of patient DNAs were established, and the genotypes were confirmed by sequencing. Thus, quinolone-resistant H. pylori strains can be easily and quickly diagnosed before treatment, which will help to avoid the administration of ineffective drug regimes