A new type of Cu 2+ fluorescent sensor, coucage, has been prepared with a photosensitive nitrophenyl group incorporated into the backbone of a coumarin-tagged tetradentate ligand. Coucage provides a selective fluorescence response for Cu 2+ over other biologically relevant metal ions. Coordination of Cu 2+ dims the fluorescence output until irradiation with UV light cleaves the ligand backbone, which relieves the copper-induced quenching to provide a turn-on response. Experiments in live MCF-7 cells show that coucage can be used for detecting changes in intracellular Cu 2+ upon the addition of excess exogenous copper. If improvements can be made to increase its affinity for copper, this new type of turn-on sensor could be used as a tool for visualizing the cellular distribution of labile copper to gain insight into the mechanisms of copper trafficking.Copper, the third most abundant transition metal in the human body, plays a critical role in many fundamental physiological processes; however, it also catalyzes the production of highly reactive oxygen species that damage biomolecules.1 Due to copper's dual nature, cells have developed strict regulatory processes to control its cellular distribution.1 Alterations in copper homeostasis are linked to neurodegenerative diseases such as Menkes and Wilson diseases, Alzheimer's, familial amyotrophic lateral sclerosis, and prion diseases. 2 Being able to visualize the cellular distribution of copper in both its physiological oxidation states, Cu + and Cu 2+ , would offer insight into how cells acquire, maintain, and utilize copper while suppressing its toxicity. Whereas reliable fluorescence sensors exist for Cu + , there are fewer options for detecting Cu 2+ in living cells.3 A common strategy in designing fluorescent probes for metal ions is to link a ligand to a fluorophore such that metal binding causes an increase in fluorescence only in response to the target ion. Cell permeable fluorescent sensors have proven useful for investigating intracellular metal ion distribution, particularly for Ca 2+ ,4 Zn 2+, 5 and Cu + .6 The development of this type of "turn-on" sensor for Cu 2+ , however, is hampered by the fluorescence quenching effect of this paramagnetic metal ion. As a consequence, many Cu 2+ sensors have a "turn-off" mechanism,7 which is generally less sensitive, gives false-positive results, and offers limited spatial resolution. Several examples of turn-on sensors have appeared recently,3 , 8 but limitations include sensing mechanisms that operate only in organic solvent or at non-physiological pH,8a-d low quantum yields in aqueous solution,8e or potential off-target responses.8f-i Therefore, there is a need to develop new strategies that provide a fluorescent turn-on response in order to investigate intracellular Cu 2+ . We present here coucage, a new type of fluorescent sensor that uses UV light to uncage a Cu 2+ -dependent fluorescence response.Katherine.franz@duke.edu. Supporting Information Available: Full experimental details, including synthesis...
Thymectomy was well tolerated by this group of children. There was clinical improvement after thymectomy in two thirds of the AchR-Ab-positive generalized myasthenia gravis patients. Thymic pathology was seen in less than one third of the patients who underwent thymectomy, with thymic hyperplasia being common. Further studies are necessary to determine whether thymectomy is indicated for all children with generalized JMG. More information about the immunologic, genetic, and molecular differences between patients may determine the best treatment for individual patients.
Introduction and hypothesis The objective was to assess whether telemedicine-based follow-up is equivalent to office-based follow-up in the early postoperative period after routine synthetic midurethral sling placement. Methods This is a prospective, international, multi-institutional, randomized controlled trial. Patients undergoing synthetic midurethral sling placement were randomized to 3-week postoperative telemedicine versus office-based follow-up. The primary outcome was the rate of unplanned events. Secondary outcomes included patient satisfaction, crossover from telemedicine to office-based follow-up, and compliance with 3- to 5-month office follow-up. Results We included 238 patients (telemedicine: 121 vs office: 117). No differences in demographics or medical comorbidities were noted between the study groups ( p = 0.09–1.0). No differences were noted in unplanned events: hospital admission, emergency department visit, or unplanned office visit or call (14% vs 12.9%, p = 0.85) or complications (9.9% vs 8.6%, p = 0.82). Both groups were equally “very satisfied” with their surgical outcomes (71.1% vs 69%, p = 0.2). Telemedicine patients were more compliant with 3- to 5-month office follow-up (90.1% vs 79.3%, p = 0.04). Conclusions After synthetic midurethral sling placement, telemedicine follow-up is a safe patient communication option in the early postoperative period. Telemedicine patients reported no difference in satisfaction compared with office-based follow-up but had greater compliance with 3- to 5-month follow-up.
remaining OAB patients, N[87). Omnibus F-tests showed the groups differed on a number of variables including AUA-SI, ICIQ, UDI, IIQ, and GUPI, with C having worse symptoms than A & B.CONCLUSIONS: Our results demonstrate that latent class trajectory models of urge ratings during natural bladder filling reveals subtypes of OAB differing in clinical symptoms. Further analyses on rs-fMRI may reveal differences in pathophysiology between the three groups.
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