University of Lorraine

About: University of Lorraine is a education organization based out in Nancy, France. It is known for research contribution in the topics: Population & Context (language use). The organization has 11942 authors who have published 25010 publications receiving 425227 citations. The organization is also known as: Lorraine University.

Ciliary Neurotrophic Factor Cell-Based Delivery Prevents Synaptic Impairment and Improves Memory in Mouse Models of Alzheimer's Disease

Abstract: The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta (Abeta) oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of Abeta oligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances. Most importantly, CNTF led to full recovery of cognitive functions associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive Abeta-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.

Management of cardiogenic shock complicating myocardial infarction

Abstract: Up to 10% of acute coronary syndromes are complicated by cardiogenic shock (CS) with contemporary mortality rates of 40–50%. The extent of ischemic myocardium has a profound impact on the initial, in-hospital, and post-discharge management and prognosis in this patient population. Individualized patient risk assessment plays an important role in determining appropriate revascularization, drug treatment with inotropes and vasopressors, mechanical circulatory support, intensive care support of other organ systems, hospital level of care triage, and allocation of clinical resources. This review will outline the underlying causes and diagnostic criteria, pathophysiology, and treatment of CS complicating acute coronary syndromes with a focus on (a) potential therapeutic issues from the perspective an interventional cardiologist, an emergency physician, and an intensive care physician, (b) the type of revascularization, and (c) new therapeutic advancements in pharmacologic and mechanical percutaneous circulatory support.

Conformational transitions of the serotonin 5-HT3receptor.

Abstract: The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane1,2; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression3. In spite of several reported pLGIC structures4-8, no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT3 receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3.2 A to 4.5 A. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody5 or without ligand9. The other structures include an 'open' state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail.

Determination of the latency effects on surgical performance and the acceptable latency levels in telesurgery using the dV-Trainer(®) simulator.

Abstract: BACKGROUND: The primary limitation of telesurgery is the communication latency. Accurate and detailed data are lacking to reveal the latency effects on surgical performance; furthermore, the maximum acceptable latency in telesurgery remains unclear. METHODS: Sixteen medical students performed an energy dissection exercise and a needle-driving exercise on the robotic simulator dV-Trainer(®), and latencies varying between 0 and 1,000 ms with a 100-ms interval were randomly and blindly presented. Task completion time, instrument motion, and errors were automatically recorded. The difficulty, security, precision, and fluidity of manipulation were self-scored by subjects between 0 and 4 (0 the best, 2 moderate, and 4 the worst). RESULTS: Task completion time, motion, and errors increased gradually as latency increased. An exponential regression was fit to the mean times and motions (R (2) > 0.98). Subjective scorings of the four items were similar. The mean scores were less than 1 at delays ≤200 ms, then increased from 1 to 2 at 300-700 ms, and finally approached 3 at delays above. In both exercises, latencies ≤300 ms were judged to be safe by all and 400-500 ms were accepted by 66-75 % of subjects. Less than 20 % of subjects accepted delays ≥800 ms. CONCLUSIONS: The surgical performance deteriorates in an exponential way as the latency increases. The delay impact on instrument manipulation is mild at 0-200 ms, then increases from small to large at 300-700 ms, and finally becomes very large at 800-1,000 ms. Latencies ≤200 ms are ideal for telesurgery; 300 ms is also suitable; 400-500 ms may be acceptable but are already tiring; and 600-700 ms are difficult to deal with and only acceptable for low risk and simple procedures. Surgery is quite difficult at 800-1,000 ms, telementoring would be a better choice in this case.