Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue

Abstract.: The dystrophin glycoprotein complex (DGC) is a multimeric protein assembly associated with either the X-linked cytoskeletal protein dystrophin or its autosomal homologue utrophin. In striated muscle cells, the DGC links the extracellular matrix to the actin cytoskeleton and mediates three major functions: structural stability of the plasma membrane, ion homeostasis, and transmembrane signaling. Mutations affecting the DGC underlie major forms of congenital muscle dystrophies. The DGC is prominent also in the central and peripheral nervous system and in tissues with a secretory function or which form barriers between functional compartments, such as the blood-brain barrier, choroid plexus, or kidney. A considerable molecular heterogeneity arises from cell-specific expression of its constituent proteins, notably short C-terminal isoforms of dystrophin. Experimentally, the generation of mice carrying targeted gene deletions affecting the DGC has clarified the interdependence of DGC proteins for assembly of the complex and revealed its importance for brain development and regulation of the 'milieu intérieur. Here, we focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discuss the role of dystrophin isoforms and utrophin for assembly of the complex in these tissue

Operative versus non-operative management of rib fractures in flail chest after cardiopulmonary resuscitation manoeuvres

OBJECTIVES: Blunt chest trauma after mechanical resuscitation manoeuvres appears to have a significant impact on the often complicated course. Due to a lack of data in the literature, the purpose of this study was to investigate the feasibility and immediate outcome of chest wall stabilization for flail chest in this vulnerable patient population. METHODS: We retrospectively reviewed the medical records of patients after cardiopulmonary resuscitation between January 2014 and December 2018 who were diagnosed with flail chest. We attempted to compare patients after surgery with those after conservative treatment. RESULTS: Of a total of 56 patients with blunt chest trauma after mechanical resuscitation and after coronary angiography, 25 were diagnosed with flail chest. After the exclusion of 2 patients because of an initial decision to palliate, 13 patients after surgical stabilization could be compared with 10 patients after conservative therapy. Although there was no significant difference in the total duration of ventilatory support, there was a significant advantage when the time after stabilization to extubation was compared with the duration of ventilation in the conservative group. The presence of pulmonary contusion, poor Glasgow Coma Scale score or the development of pneumonia negatively affected the outcome, but additional sternal fracture did not. CONCLUSIONS: Surgical stabilization for chest wall instability is well tolerated even by this vulnerable patient population. Our results should be used for further randomized controlled approaches. It is necessary to evaluate the situation with all parameters in an interdisciplinary manner and to decide on a possible surgical therapy at an early stage if possible

Nearest Neighbor Connectivity in Two-Dimensional Multihop MANETs

A Mobile Ad Hoc Network (MANET) is characterized to be a network with free, cooperative, and dynamic nodes, self-organized in a random topology, without any kind of infrastructure, where the communication between two nodes usually occurs using multihop paths. The number of hops used in the multihop path is an important metric for the design and performance analysis of routing protocols in MANETs. In this paper, we derive the probability distribution of the hop count of a multihop path between a source node and a destination node, fixed at a known distance from each other, and when a fixed number of nodes are uniformly distributed in a region of interest. This distribution is obtained by the Poisson randomization method. To obtain the multihop path, we propose a novel routing model in which the nearest distance routing protocol (NR) is analyzed. Numerical results are obtained to evaluate the performance of the NR

Standardized visual EEG features predict outcome in patients with acute consciousness impairment of various etiologies.

Early prognostication in patients with acute consciousness impairment is a challenging but essential task. Current prognostic guidelines vary with the underlying etiology. In particular, electroencephalography (EEG) is the most important paraclinical examination tool in patients with hypoxic ischemic encephalopathy (HIE), whereas it is not routinely used for outcome prediction in patients with traumatic brain injury (TBI). Data from 364 critically ill patients with acute consciousness impairment (GCS ≤ 11 or FOUR ≤ 12) of various etiologies and without recent signs of seizures from a prospective randomized trial were retrospectively analyzed. Random forest classifiers were trained using 8 visual EEG features-first alone, then in combination with clinical features-to predict survival at 6 months or favorable functional outcome (defined as cerebral performance category 1-2). The area under the ROC curve was 0.812 for predicting survival and 0.790 for predicting favorable outcome using EEG features. Adding clinical features did not improve the overall performance of the classifier (for survival: AUC = 0.806, p = 0.926; for favorable outcome: AUC = 0.777, p = 0.844). Survival could be predicted in all etiology groups: the AUC was 0.958 for patients with HIE, 0.955 for patients with TBI and other neurosurgical diagnoses, 0.697 for patients with metabolic, inflammatory or infectious causes for consciousness impairment and 0.695 for patients with stroke. Training the classifier separately on subgroups of patients with a given etiology (and thus using less training data) leads to poorer classification performance. While prognostication was best for patients with HIE and TBI, our study demonstrates that similar EEG criteria can be used in patients with various causes of consciousness impairment, and that the size of the training set is more important than homogeneity of ACI etiology

Connectivity of Soft Random Geometric Graphs Over Annuli

Nodes are randomly distributed within an annulus (and then a shell) to form a point pattern of communication terminals which are linked stochastically according to the Rayleigh fading of radio-frequency data signals. We then present analytic formulas for the connection probability of these spatially embedded graphs, describing the connectivity behaviour as a dense-network limit is approached. This extends recent work modelling ad hoc networks in non-convex domains.Comment: 12 pages, 6 figure

Full Connectivity: Corners, edges and faces

We develop a cluster expansion for the probability of full connectivity of high density random networks in confined geometries. In contrast to percolation phenomena at lower densities, boundary effects, which have previously been largely neglected, are not only relevant but dominant. We derive general analytical formulas that show a persistence of universality in a different form to percolation theory, and provide numerical confirmation. We also demonstrate the simplicity of our approach in three simple but instructive examples and discuss the practical benefits of its application to different models.Comment: 28 pages, 8 figure

The real foundation of fictional worlds

I argue that judgements of what is ‘true in a fiction’ presuppose the Reality Assumption: the assumption that everything that is (really) true is fictionally the case, unless excluded by the work. By contrast with the more familiar Reality Principle, the Reality Assumption is not a rule for inferring implied content from what is explicit. Instead it provides an array of real-world truths that can be used in such inferences. I claim that the Reality Assumption is essential to our ability to understand stories, drawing on a range of empirical evidence that demonstrates our reliance on it in narrative comprehension. However, the Reality Assumption has several unintuitive consequences, not least that what is fictionally the case includes countless facts that neither authors nor readers could (or should) ever consider. I argue that such consequences provide no reason to reject the Reality Assumption. I conclude that we should take fictions, like non-fictions, to be about the real world

Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia

BACKGROUND: We demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH. METHODS: SAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO(2)) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS). RESULTS: Seven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO(2) time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died. CONCLUSION: Administration of iNO in SAH patients is safe. These results call for a larger prospective evaluation