Right coronary artery-coronary sinus fistula diagnosed by three-dimensional echocardiography

Right coronary artery-coronary sinus fistula is a very rare congenital anomaly in which a right coronary artery fistula drains into the right atrium, right ventricle, or pulmonary artery. A right coronary artery-coronary sinus fistula was diagnosed in a 44-year-old man by three-dimensional echocardiography and confirmed by computed tomography angiography and surgery. Relevant published experience in diagnosing this kind of anomaly is summarized.     

Fidelity and sustainability of Mouth Care Without a Battle and lessons for other innovations in care

There are countless efficacious interventions that improve outcomes when conducted in controlled situations. Many fewer are effective when implemented in real-world situations, largely because they are not implemented with fidelity. Still fewer are sustained over time, for reasons including lack of institutional support and fit with existing values, among others. It is especially important to examine fidelity and sustainability when efficacious interventions are being implemented, because these interventions are the ones that hold the most promise. This project examined the fidelity and sustainability of Mouth Care Without a Battle (MCWB), an evidence-based program conducted in a two-year cluster randomized trial in 14 nursing homes. Results that triangulated two sources of data indicated that fidelity decreased after the first year; they provide guidance to promote fidelity and sustainability of this and other new care practices in nursing homes, including ongoing education, coaching, evaluation, feedback, and sufficient resources.     

Effectiveness of online dementia caregivers training programs: A systematic review

Over the next thirty years, Alzheimer's disease rates will increase alongside global aging. With the anticipated increase in demand, knowledgeable and skilled dementia caregivers will be in need across the long-term care spectrum. This study is a systematic review of online dementia-based training programs for formal and informal caregivers conducted to analyze evidence for using online training programs. We used the Preferred Reporting Items for Systematic Reviews (PRISMA) method. Methodological quality was assessed by the Cochrane Collaboration Back Review Group criteria. No previously published systematic review has analyzed online dementia training programs among both formal and informal caregivers. A systematic search of Web of Science, PsychInfo, and PubMed resulted in a final sample of (N = 19) studies. Results suggest that online interventions improve the condition and preparedness of caregivers, but future evaluations should consider study designs with multiple time points, control groups, and content that is personalized and interactive.     

Postural effect on gait characteristics by using rolling walkers

This study was to examine the effect of leaning-forward posture (LFP) on gait parameters while using a rolling walker (RW).A cross-sectional study was conducted in which 23 older female adults were asked to walk with a RW on the GaitRite walkway in two posture situations: upright posture, and LFP caused by pushing the RW forward and then following the RW. The temporal and spatial gait parameters were obtained for data analysis.Results showed that compared with the upright posture, participants with LFP demonstrated significantly increased cadence, decreased velocity and gait cycle time (both swing and stance time decreased). Of spatial parameters, both step and stride length significantly decreased, but the base of support increased significantly.These indicate that LFP during ambulation with a RW could lead participants to a shuffling-like (many steps on short distance) gait pattern. They may help clinicians find proper rehabilitation interventions and appropriate patient education for this specific postural presentation.     

A mixed methods evaluation of got care!

This study aimed to assess the relationship between an Interprofessional Collaborative Practice (IPCP) intervention for community-dwelling older adults, Geriatric Outreach and Training with Care! (GOT Care!), and the observed 26% reduction in Emergency Department (ED) visits for the 51 older adult participants. A convergent parallel mixed-methods design was utilized. Demographic data and ED visit data were collected and analyzed using paired-samples t-tests, poisson regression and generalized poisson regression. Stakeholder perspectives were assessed via emailed open-ended surveys and analyzed using content analysis. The quantitative results were transformed into trends that were compared and contrasted with the qualitative themes. The results were consistent with the current literature that IPCP models may have a greater impact on older adults with certain demographic characteristics such as polypharmacy, diabetes and prior ED use, while nursing was identified as an ideal leader for IPCP teams.     

Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes

A new type of drug-delivery system (DDS) was constructed, in which the anti-cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm) BaGdF₅:Yb³⁺/Tm³⁺ based upconversion nanoparticles (UCNPs). This multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X-ray computed tomography imaging capabilities. The DOX can be selectively released by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit obvious cytotoxic effect on HeLa cells. Moreover, to improve the upconversion luminescence intensity, core–shell structured UCNPs were constructed. The in vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show bright emission with high contrast. In addition, these UCNPs were further explored for T₁-weighted magnetic resonance (MR) and X-ray computed tomography (CT) imaging in vitro. Long-term in vivo toxicity studies indicated that mice intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any apparent adverse effects to their health. The results indicate that this multifunctional drug-delivery system with optimized size, excellent optical/MR/CT trimodal imaging capabilities, and pH-triggered drug release property is expected to be a promising platform for simultaneous cancer therapy and bioimaging.     

Gadolinium complex and phosphorescent probe-modified NaDyF4 nanorods for T1- and T2-weighted MRI/CT/phosphorescence multimodality imaging

To compensate for the deficiencies of individual imaging modalities, lanthanide-based nanoparticles are ideal building blocks for multifunctional contrast agents. Herein, oleic acid-coated NaDyF₄ nanorods (DyNPs) were synthesized by the hydrothermal method, and then coated with α-cyclodextrin (α-CD) and modified with gadolinium complex (Gd-DTPA) to obtain hydrophilic and functionalized nanoparticles (DyNPs-Gd). By loading the phosphorescent probe (iridium-complex) within the surface hydrophobic layer, the developed nanophosphors (DyNPs-Gd-Ir) could be further applied in phosphorescent cell labeling. The Dy in the host induces a high X-ray absorption ability for X-ray computed tomography (CT) and negative enhancement for T₂-weighted magnetic resonance imaging (MRI), whereas positive contrast for T₁-weighted MRI results from the Gd-DTPA. DyNPs-Gd-Ir has been successfully applied to T₁- and T₂-weighted MRI/CT in vivo. Toxicity studies demonstrated that DyNPs-Gd-Ir exhibited low toxicity to living systems. Therefore, DyNPs-Gd-Ir could be a platform for next-generation contrast agents for T₁- and T₂-weighted MRI/CT/phosphorescence multimodal imaging.     

A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy

Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here we show that exosomes, endogenous nano-sized membrane vesicles secreted by most cell types, can deliver chemotherapeutics such as doxorubicin (Dox) to tumor tissue in BALB/c nude mice. To reduce immunogenicity and toxicity, mouse immature dendritic cells (imDCs) were used for exosome production. Tumor targeting was facilitated by engineering the imDCs to express a well-characterized exosomal membrane protein (Lamp2b) fused to αv integrin-specific iRGD peptide (CRGDKGPDC). Purified exosomes from imDCs were loaded with Dox via electroporation, with an encapsulation efficiency of up to 20%. iRGD exosomes showed highly efficient targeting and Dox delivery to αv integrin-positive breast cancer cells in vitro as demonstrated by confocal imaging and flow cytometry. Intravenously injected targeted exosomes delivered Dox specifically to tumor tissues, leading to inhibition of tumor growth without overt toxicity. Our results suggest that exosomes modified by targeting ligands can be used therapeutically for the delivery of Dox to tumors, thus having great potential value for clinical applications.     

Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery,enzyme-stimulated release and MRI

A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic–hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T₂-weighted imaging. Our results suggest that the gelatin encapsulated Fe₃O₄ nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor.     

A multi-stimuli responsive gold nanocage–hyaluronic platform for targeted photothermal and chemotherapy

Noninvasive and pinpointed intracellular drug release that responds to multiple stimulus is still a formidable challenge for cancer therapy. Herein, we reported a multi-stimuli responsive platform based on drug loaded gold nanocages @ hyaluronic acid (AuNCs-HA) for pinpointed intracellular drug release. These well-prepared nanohybrids could specifically recognize cancer cells via HA-CD44 interactions and be efficiently endocytosed by receptor-mediated process. Subsequently, the coated HA molecules could be degraded in lysosomes, resulting in the release of encapsulated drug. In addition, by taking advantage of the excellent photothermal properties, the AuNCs could accelerate the release of encapsulated drug and induce a higher therapeutic efficacy upon near-infrared (NIR) irradiation. In vitro results confirmed that the encapsulated drug could only be pinpointedly released in intracellular environments, which permitted high therapeutic efficacy against cancer cells and minimized the side effects. Importantly, as compared to that of the two therapies independently, a complete inhibition of tumor growth treated with the combination of chemotherapy and photothermal therapy was observed in vivo. Taken together, our present study provides new insights into developing pinpointed, multi-stimuli responsive intracellular drug release systems for synergistic cancer therapy.