Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: A seven case series

Background: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Results: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. Conclusions: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling

Complaints handling in hospitals: an empirical study of discrepancies between patients' expectations and their experiences

<p>Abstract</p> <p>Background</p> <p>Many patients are dissatisfied with the way in which their complaints about health care are dealt with. This study tested the assumption that this dissatisfaction consists – in part at least – of unmet expectations.</p> <p>Methods</p> <p>Subjects were 279 patients who lodged a complaint with the complaints committees of 74 hospitals in the Netherlands. They completed two questionnaires; one on their expectations at the start of the complaints handling process, and one on their experiences after the complaints procedure (pre-post design; response 50%). Dependent variables are patients' satisfaction and their feeling that justice was done; independent variables are the association between patients' expectations and their experiences.</p> <p>Results</p> <p>Only 31% of the patients felt they had received justice from the complaints process.</p> <p>Two thirds of the patients were satisfied with the conduct of the complaints committee, but fewer were satisfied with the conduct of the hospital or the medical professional (29% and 18%). Large discrepancies between expectations and experiences were found in the case of doctors not admitting errors when errors had been made, and of hospital managements not providing information on corrective measures that were taken. Discrepancies collectively explained 51% of patients' dissatisfaction with the committee and one third of patients' dissatisfaction with the hospital and the professional. The feeling that justice was done was influenced by the decision on the complaint (well-founded or not), but also by the satisfaction with the conduct of the committee, the hospital management and the professional involved.</p> <p>Conclusion</p> <p>It is disappointing to observe that less than one third of the patients felt that justice had been done through the complaints handling process. This study shows that the feeling that justice had been done is not only influenced by the judgement of the complaints committee, but also by the response of the professional. Furthermore, hospitals and professionals should communicate on how they are going to prevent a recurrence of the events that led to the complaint.</p

The Elg1 Clamp Loader Plays a Role in Sister Chromatid Cohesion

Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring

Dynamical Principles of Emotion-Cognition Interaction: Mathematical Images of Mental Disorders

The key contribution of this work is to introduce a mathematical framework to understand self-organized dynamics in the brain that can explain certain aspects of itinerant behavior. Specifically, we introduce a model based upon the coupling of generalized Lotka-Volterra systems. This coupling is based upon competition for common resources. The system can be regarded as a normal or canonical form for any distributed system that shows self-organized dynamics that entail winnerless competition. Crucially, we will show that some of the fundamental instabilities that arise in these coupled systems are remarkably similar to endogenous activity seen in the brain (using EEG and fMRI). Furthermore, by changing a small subset of the system's parameters we can produce bifurcations and metastable sequential dynamics changing, which bear a remarkable similarity to pathological brain states seen in psychiatry. In what follows, we will consider the coupling of two macroscopic modes of brain activity, which, in a purely descriptive fashion, we will label as cognitive and emotional modes. Our aim is to examine the dynamical structures that emerge when coupling these two modes and relate them tentatively to brain activity in normal and non-normal states

Mediterranean-climate streams and rivers: geographically separated but ecologically comparable freshwater systems

Streams and rivers in mediterranean-climate regions (med-rivers in med-regions) are ecologically unique, with flow regimes reflecting precipitation patterns. Although timing of drying and flooding is predictable, seasonal and annual intensity of these events is not. Sequential flooding and drying, coupled with anthropogenic influences make these med-rivers among the most stressed riverine habitat worldwide. Med-rivers are hotspots for biodiversity in all med-regions. Species in med-rivers require different, often opposing adaptive mechanisms to survive drought and flood conditions or recover from them. Thus, metacommunities undergo seasonal differences, reflecting cycles of river fragmentation and connectivity, which also affect ecosystem functioning. River conservation and management is challenging, and trade-offs between environmental and human uses are complex, especially under future climate change scenarios. This overview of a Special Issue on med-rivers synthesizes information presented in 21 articles covering the five med-regions worldwide: Mediterranean Basin, coastal California, central Chile, Cape region of South Africa, and southwest and southern Australia. Research programs to increase basic knowledge in less-developed med-regions should be prioritized to achieve increased abilities to better manage med-rivers