ABSTRACT
Background and Purpose: Growing evidence has shown that cognitive interventions can mitigate cognitive decline in patients with mild cognitive impairment (MCI). However, most previous cognitive interventions have been group-based programs. Due to their intrinsic limitations, group-based programs are not widely used in clinical practice. Therefore, we have developed a tablet-based cognitive intervention program. This preliminary study investigated the feasibility and effects of a 12-week structured tablet-based program on cognitive function in patients with MCI. Methods: We performed a single-arm study on 24 patients with MCI. The participants underwent a tablet-based cognitive intervention program 5 times a week over a 12-week period. The primary outcome was changes in cognitive function, measured using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K). Outcomes were evaluated at baseline, within two weeks of the last program (post-intervention), and at the six-month follow-up session. Results: The completion rate of the tablet-based program was 83.3% in patients with MCI. The program improved cognitive function based on the CERAD-K total score (p=0.026), which was maintained for at least three months (p=0.004). There was also an improvement in the depression scale score (p=0.002), which persisted for three months (p=0.027). Conclusions: Our 12-week structured tablet-based program is feasible for patients with MCI. Furthermore, although further studies with a double-arm design are required, the program appears to be an effective strategy to prevent cognitive decline in patients with MCI.
ABSTRACT
Hydrogen sulfide is a critical biological messenger, but few biologically compatible methods are available for its detection in vivo. Here, we describe the design and synthesis of a novel azide-functionalized near-infrared probe, NIR-Az, for a hydrogen sulfide assay in which a self-immolative linker is incorporated between the azide moiety and phenolic dihydroxanthene fluorophore from a cyanine dye. A large "turn-on" near-infrared fluorescence signal results from the reduction of the azide group of the fluorogenic moiety to an amine, in which the self-immolative linker also enhances the accessibility of NIR-Az to hydrogen sulfide. NIR-Az can select hydrogen sulfide from among 16 analytes, including cysteine, glutathione, and homocysteine. By exploiting the superior properties of NIR-Az, such as its good biocompatibility and rapid cell internalization, we successfully demonstrated its usefulness in monitoring both the concentration- and time-dependent variations of hydrogen sulfide in living cells and animals (detection limit less than 0.26µM), thereby providing a powerful approach for probing hydrogen sulfide chemistry in biological systems.
Subject(s)
Biosensing Techniques , Hydrogen Sulfide/isolation & purification , Spectrometry, Fluorescence , Animals , Azides/chemistry , Cysteine/chemistry , Cysteine/isolation & purification , Fluorescence , Fluorescent Dyes/chemistry , Glutathione/chemistry , Glutathione/isolation & purification , Hydrogen Sulfide/chemistryABSTRACT
Hydrogen sulfide (H2S) is an important biological messenger, but few biologically-compatible methods are available for its detection in aqueous solution. Herein, we report a highly water-soluble naphthalimide-based fluorescent probe (L1), which is a highly versatile building unit that absorbs and emits at long wavelengths and is selective for hydrogen sulfide over cysteine, glutathione, and other reactive sulfur, nitrogen, and oxygen species in aqueous solution. We describe turn-on fluorescent probes based on azide group reduction on the fluorogenic 'naphthalene' moiety to fluorescent amines and intracellular hydrogen sulfide detection without the use of an organic solvent. L1 and L2 were synthetically modified to functional groups with comparable solubility on the N-imide site, showing a marked change in turn-on fluorescent intensity in response to hydrogen sulfide in both PBS buffer and living cells. The probes were readily employed to assess intracellular hydrogen sulfide level changes by imaging endogenous hydrogen sulfide signal in RAW264.7 cells incubated with L1 and L2. Expanding the use of L1 to complex and heterogeneous biological settings, we successfully visualized hydrogen sulfide detection in the yolk, brain and spinal cord of living zebrafish embryos, thereby providing a powerful approach for live imaging for investigating chemical signaling in complex multicellular systems.
