Cushing's Disease Management: Glimpse Into 2051

Major advancements are expected in medicine and healthcare in the 21st century- "Digital Age", mainly due to the application of data technologies and artificial intelligence into healthcare. In this perspective article we share a short story depicting the future Cushings' Disease patient and the postulated diagnostic and management approaches. In the discussion, we explain the advances in recent times which makes this future state plausible. We postulate that endocrinology care will be completely reinvented in the Digital Age

Coronal thick CT reconstruction: an alternative for initial chest radiography in trauma patients

It has been proposed that the imaging workup of trauma patients be accelerated by omitting the initial chest radiography (CR) and directly performing a computed tomography (CT); however, the baseline CR is then lacking. The purpose of this study was to assess if coronal thick reconstructions generated from chest CT could present an adequate alternative for CR. Sixty trauma patients underwent bedside CR and multidetector row chest CT in the emergency room. The image quality of thoracic anatomical structures, the diagnostic accuracy for chest pathology, and the depiction of indwelling devices were assessed on both modalities. Main pulmonary arteries and perihilar bronchi were equally visualized with both modalities. Central bronchi, retrocardial lung parenchyma, diaphragm, descending aorta, and vertebral pedicles were better visualized on thick CT reconstructions, whereas peripheral lung vessels were better depicted on CR (p<0.05). The accuracy to delineate various pathological findings did not differ between both modalities, except for a higher sensitivity to diagnose bronchial cuffing on CR (p<0.05). The location of indwelling devices was similarly and correctly depicted with both modalities. Coronal thick CT reconstructions provide a similar image quality and diagnostic accuracy compared with CR. These reconstructions may serve as an equivalent baseline image in trauma patients in whom emergency radiological evaluation has to be accelerate

Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells

Clonogenic neural stem cells (NSCs) are self-renewing cells that maintain the capacity to differentiate into brain-specific cell types, and may also replace or repair diseased brain tissue. NSCs can be directly isolated from fetal or adult nervous tissue, or derived from embryonic stem cells. Here, we describe the efficient conversion of human adult bone marrow stromal cells (hMSC) into a neural stem cell-like population (hmNSC, for human marrow-derived NSC-like cells). These cells grow in neurosphere-like structures, express high levels of early neuroectodermal markers, such as the proneural genes NeuroD1, Neurog2, MSl1 as well as otx1 and nestin, but lose the characteristics of mesodermal stromal cells. In the presence of selected growth factors, hmNSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Clonal analysis demonstrates that individual hmNSCs are multipotent and retain the capacity to generate both glia and neurons. Our cell culture system provides a powerful tool for investigating the molecular mechanisms of neural differentiation in adult human NSCs. hmNSCs may therefore ultimately help to treat acute and chronic neurodegenerative diseases

Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)

Background Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography. Methods We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP. Results In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI. Conclusion Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI

Impact of preoperative positron emission tomography in patients with severely impaired LV-function undergoing surgical revascularization

In patients with ischemic cardiomyopathy, coronary artery bypass grafting (CABG) offers an important therapeutic option but is still associated with high perioperative mortality. Although previous studies suggest a benefit from revascularization for patients with defined viability by a non-invasive technique, the role of viability assessment to determine suitability for revascularization in patients with ischemic cardiomyopathy has not yet been defined. This study evaluates the hypothesis that the use of PET imaging in the decision-making process for CABG will improve postoperative patient survival. We reviewed 476 patients with ischemic cardiomyopathy (LV ejection fraction ≤0.35) who were considered candidates for CABG between 1994 and 2004 on the basis of clinical presentation and angiographic data. In a Standard Care Group, 298 patients underwent CABG. In a second PET-assisted management group of 178 patients, 152 patients underwent CABG (PET-CABG) and 26 patients were excluded from CABG because of lack of viability (PET-Alternatives). Primary endpoint was postoperative survival. There were two in hospital deaths in the PET-CABG (1.3%) and 30 (10.1%) in the Standard Care Group (P = 0.018). The survival rate after 1, 5 and 9.3 years was 92.0, 73.3 and 54.2% in the PET-CABG and 88.9, 62.2 and 35.5% in the Standard Care Group, respectively (P = 0.005). Cox-regression analysis revealed a significant influence on long-term survival of patient selection by viability assessment via PET (P = 0.008), of LV-function (P = 0.017), and age >70 (P = 0.016). Preoperative assessment of myocardial viability via PET identifies patients, who will benefit most from CABG

The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis

Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of β-actin mRNA and fewer dendritic β-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons

The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1

We previously demonstrated that the transcription factor Pax4 is important for β-cell replication and survival in rat islets. Herein, we investigate Pax4 expression in islets of non-diabetic and diabetic donors, its regulation by mitogens, glucose and the incretin GLP-1 and evaluate its effect on human islet proliferation. Pax4 expression was increased in islets derived from Type 2 diabetic donors correlating with hyperglycaemia. In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels. Glucose-induced Pax4 expression was abolished by the inhibitors LY294002, PD98050 or H89. Surprisingly, increases in Pax4 expression did not prompt a surge in human islet cell replication. Furthermore, expression of the proliferation marker gene Id2 remained unaltered. Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets. In contrast, overexpression of mouse Pax4 induced human islet cell proliferation. Treatment of islets with 5-Aza-2′-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression. Human Pax4 DNA binding activity was found to be lower than that of the mouse homologue. Thus, human pax4 gene expression is epigenetically regulated and induced by physiological stimuli through the concerted action of multiple signalling pathways. However, it is unable to initiate the transcriptional replication program likely due to post-translational modifications of the protein. The latter highlights fundamental differences between human and rodent islet physiology and emphasizes the importance of validating results obtained with animal models in human tissue

Coronal thick CT reconstruction: an alternative for initial chest radiography in trauma patients

It has been proposed that the imaging workup of trauma patients be accelerated by omitting the initial chest radiography (CR) and directly performing a computed tomography (CT); however, the baseline CR is then lacking. The purpose of this study was to assess if coronal thick reconstructions generated from chest CT could present an adequate alternative for CR. Sixty trauma patients underwent bedside CR and multidetector row chest CT in the emergency room. The image quality of thoracic anatomical structures, the diagnostic accuracy for chest pathology, and the depiction of indwelling devices were assessed on both modalities. Main pulmonary arteries and perihilar bronchi were equally visualized with both modalities. Central bronchi, retrocardial lung parenchyma, diaphragm, descending aorta, and vertebral pedicles were better visualized on thick CT reconstructions, whereas peripheral lung vessels were better depicted on CR (p<0.05). The accuracy to delineate various pathological findings did not differ between both modalities, except for a higher sensitivity to diagnose bronchial cuffing on CR (p<0.05). The location of indwelling devices was similarly and correctly depicted with both modalities. Coronal thick CT reconstructions provide a similar image quality and diagnostic accuracy compared with CR. These reconstructions may serve as an equivalent baseline image in trauma patients in whom emergency radiological evaluation has to be accelerate