Compassion Meditation for Distressed Older Veterans: A Feasibility Study.

OBJECTIVES: Older Veterans are at elevated risk for psychological distress and may encounter barriers to accessing mental health services. Compassion Meditation (CM) promotes positive emotions and outcomes among distressed individuals; thus, we conducted a preliminary feasibility study of CM among distressed older Veterans. METHODS: Participants included 25 Veterans aged 55+ (M = 69.0, SD = 10.6) with anxiety and/or depressive symptoms, recruited from primary care, mostly male (76.0%), and White (60.0%). CM consisted of 10 groups, which were transitioned from in-person to telehealth due to COVID-19. Feasibility indices included rates of intervention initiation and completion, and attendance. Participants completed measures of symptom severity and well-being pre- and post-intervention. RESULTS: Of 25 enrolled participants, 88.0% (n = 22) attended at least one session, and 52% (n = 13) completed the intervention (attended six or more sessions). Among intervention completers, the average number of sessions attended was 9.46. Seven Veterans withdrew from intervention due to difficulties engaging via telehealth. CONCLUSIONS: These findings support the feasibility of CM training in older Veterans with psychological distress, though dropouts highlighted potential need for additional strategies to facilitate telehealth participation. CLINICAL IMPLICATIONS: Older Veterans appear amenable to meditation-based practices, provided they are easy to access.

Modular Synthesis of Heterobenzylic Amines via Carbonyl Azinylative Amination.

Transformations enabling the synthesis of α-alkyl, α'-2-azinyl amines by addition of 2-heteroaryl-based nucleophiles to in situ-generated and non-activated alkyl-substituted iminium ions are extremely rare. Approaches involving classical 2-azinyl organometallics, such as the corresponding Grignard reagents, often fail to produce the desired products. Here, we report an operationally straightforward solution to this problem through the development of a multicomponent coupling process wherein a soft 2-azinyl indium nucleophile, generated in situ from the corresponding 2-iodo heteroarene and indium powder, adds to an iminium ion that is also formed directly in the reaction. This modular carbonyl azinylative amination (CAzA) displays a broad scope and only a metal reductant is needed to generate a reactive 2-azinyl nucleophile. Beyond the addition to iminium ions, the 2-azinyl addition to polyfluoromethyl ketones forms the corresponding tertiary alcohols. Together, the products of these reactions possess a high degree of functionality, are typically challenging to synthesize by other methods, and contain motifs recognized as privileged in the context of pharmaceuticals and agrochemicals.

Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy.

Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP) chemotherapeutics in chemoradiation. Since the most commonly utilized chemotherapeutic with radiotherapy is cisplatin, the development of an NP cisplatin for chemoradiotherapy has the highest potential impact on this treatment. Here, we report the development of an NP comprised of polysilsesquioxane (PSQ) polymer crosslinked by a cisplatin prodrug (Cisplatin-PSQ) and its utilization in chemoradiotherapy using non-small cell lung cancer as a disease model. Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. Cisplatin-PSQ NPs were evaluated in chemoradiotherapy in vitro and in vivo. They demonstrated significantly higher therapeutic efficacy when compared to cisplatin. These results suggest that the Cisplatin-PSQ NP holds potential for clinical translation in chemoradiotherapy.

Biodegradable polysilsesquioxane nanoparticles as efficient contrast agents for magnetic resonance imaging.

Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions. The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53.8 wt% and 49.3 wt% of Gd-DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd-PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5.9 to 17.8 mMs(-1) on a per-Gd basis. Finally, the high sensitivity of the Gd-PSQ particles as T1 -weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro.

Silica-based nanoprobes for biomedical imaging and theranostic applications.

Nanoparticle-based contrast agents are attracting a great deal of attention for various biomedical imaging and theranostic applications. Compared to conventional contrast agents, nanoparticles possess several potential advantages to improve in vivo detection and to enhance targeting efficiency. Silica-based nanoprobes can be engineered to achieve longer blood circulation times, specific clearance pathways, and multivalent binding. In this tutorial review, we summarize the latest progress on designing silica-based nanoprobes for imaging and theranostic applications. The synthesis of both solid silica and mesoporous silica nanoparticles is described, along with different approaches used for surface functionalization. Special emphasis is placed on the application of silica-based nanoprobes in optical, magnetic resonance, and multimodal imaging. The latest breakthroughs in the applications of silica nanoparticles as theranostic agents are also highlighted.

Lipid-coated nanoscale coordination polymers for targeted cisplatin delivery.

Nanoscale coordination polymers (NCPs) containing a Pt(IV) cisplatin prodrug, disuccinatocisplatin, were formed by a surfactant-templated synthesis and were shown to have a prodrug loading of 8.2 wt% and a diameter of ~133 nm by dynamic light scattering. These NCPs were stabilized by coating with a DOPC/cholesterol/DSPE-Peg2K lipid layer; a release profile in phosphate buffered saline showed an initial drug release of ~25% within the first hour and no more release observed up to 192 h. The NCP was rendered target-specific for sigma receptors by addition of an AA-DSPE-Peg2K conjugate (AA = anisamide) in the lipid formulation. The AA-containing NCP showed a statistically significant decrease in IC50 (inhibitory concentration, 50%) compared to the non-targeted NCP. Enhanced uptake of the AA-containing NCP was further supported by confocal microscopy and competitive binding assays.

Coercing bisphosphonates to kill cancer cells with nanoscale coordination polymers.

Nanoscale coordination polymers containing exceptionally high loadings of bisphosphonates were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to much enhanced cytotoxicity against human lung and pancreatic cancer cells.