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

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

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

Cyber Operations RangE (CORE): Containerized Gaming Platform for Cyberoperations Competitions

Cybersecurity gaming is popularized through capture-the-flag (CTF) competitions, war games, and forensic challenges. Providing actual hands-on experience, the cybersecurity competitions have great potential to support classroom learning, professional skill development, and scenario testing. To capitalize this, the supporting gaming platforms need to overcome the following issues: i) A complex virtualized infrastructure that requires extensive resources and administration, ii) Lack of support for real-time cyberoperations within a competition environment, and iii) implementation of independent, real-time scoring system which tracks progress and determines results of the competitors. In response to these issues, we have developed Cyber Operations RangE (CORE) - a containerized cybersecurity gaming platform. This paper presents the design, implementation, and the application of the CORE platform for real-time cyberoperations competitions

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

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

Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions

Introduction: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between 'red streaks' and the adjacent normal looking squamous epithelium. Methods: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. Results: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. Conclusion: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy. Copyrigh

Differential expression of the ubiquitin-editing enzyme A20 in gastric biopsies indicates the severity of disease

A20, an ubiquitin-editing enzyme, plays a pivotal role in regulating cell signaling and immune responses. Dysregulated A20 expression has been associated with various pathological conditions, including inflammatory diseases and malignancies, where its expression levels often correlate with differing prognoses in solid tumors. This study aimed to explore the expression and cellular localization of A20 in both nonpathological and diseased human gastric tissues to gain deeper insights into its involvement in gastric pathologies. We analyzed paraffin-embedded gastric tissue samples from 326 patients. A20 expression was assessed using immunohistochemistry (IHC) with results categorized according to the Remmele and Stegner immunoreactive score (IRS). The study compared A20 expression across a spectrum of gastric pathologies, including Helicobacter pylori (HP) gastritis, autoimmune gastritis (A-gastritis), reactive gastropathy (C-gastritis), Ex-HP-gastritis, adenomas, and adenocarcinomas, with nonpathological gastric mucosa serving as a baseline. Our findings demonstrate a significant increase in A20 expression in HP-gastritis ( p  = 0.019), A-gastritis ( p  = 0.001), adenomas ( p  < 0.001), and adenocarcinomas ( p  < 0.001). Conversely, no significant differences in A20 expression were observed in C-gastritis or Ex-HP-gastritis cases