Gadolinium(III) nanoconjugate contrast agents (CAs) have distinct advantages over their small-molecule counterparts in magnetic resonance imaging. In addition to increased Gd(III) payload, a ...significant improvement in proton relaxation efficiency, or relaxivity (r 1), is often observed. In this work, we describe the synthesis and characterization of a nanoconjugate CA created by covalent attachment of Gd(III) to thiolated DNA (Gd(III)–DNA), followed by surface conjugation onto gold nanostars (DNA–Gd@stars). These conjugates exhibit remarkable r 1 with values up to 98 mM–1 s–1. Additionally, DNA–Gd@stars show efficient Gd(III) delivery and biocompatibility in vitro and generate significant contrast enhancement when imaged at 7 T. Using nuclear magnetic relaxation dispersion analysis, we attribute the high performance of the DNA–Gd@stars to an increased contribution of second-sphere relaxivity compared to that of spherical CA equivalents (DNA–Gd@spheres). Importantly, the surface of the gold nanostar contains Gd(III)–DNA in regions of positive, negative, and neutral curvature. We hypothesize that the proton relaxation enhancement observed results from the presence of a unique hydrophilic environment produced by Gd(III)–DNA in these regions, which allows second-sphere water molecules to remain adjacent to Gd(III) ions for up to 10 times longer than diffusion. These results establish that particle shape and second-sphere relaxivity are important considerations in the design of Gd(III) nanoconjugate CAs.
We report the design of a nanoconstruct that can function as a cell-type independent agent by targeting the ubiquitous protein nucleolin. Gold nanostars (AuNS) loaded with high densities of ...nucleolin-specific DNA aptamer AS1411 (Apt-AuNS) produced anticancer effects in a panel of 12 cancer lines containing four representative subcategories. We found that the nanoconstructs could be internalized by cancer cells and trafficked to perinuclear regions. Apt-AuNS resulted in downregulation of antiapoptotic Bcl-2 mRNA expression by ca. 200% compared to cells without the nanoconstructs. The caspase 3/7 activity (apoptosis) and cell death in cancer cells treated with Apt-AuNS increased by 1.5 times and by ca. 17%, respectively, compared to cells treated with free AS1411 at over 10 times the concentration. Moreover, light-triggered release of aptamer from the AuNS further enhanced the in vitro efficacy of the nanoconstructs in the cancer line panel with a 2-fold increase in caspase activity and a 40% decrease in cell viability compared to treatment with Apt-AuNS only. In contrast, treatments of the nanoconstructs with or without light-triggered release on a panel of normal cell lines had no adverse effects.
This paper describes how differences in the dynamics of targeting and nontargeting constructs can provide information on nanoparticle (NP)–cell interactions. We probed translational and rotational ...dynamics of functionalized Au nanostar (AuNS) nanoconstructs interacting with cells in serum-containing medium. We found that AuNS with targeting ligands had a larger dynamical footprint and faster rotational speed on cell membranes expressing human epidermal growth factor receptor 2 (HER-2) receptors compared to that of AuNS with nontargeting ligands. Targeting and nontargeting nanoconstructs displayed distinct membrane dynamics despite their similar protein adsorption profiles, which suggests that targeted interactions are preserved even in the presence of a protein corona. The high sensitivity of single-NP dynamics can be used to compare different nanoconstruct properties (such as NP size, shape, and surface chemistry) to improve their design as delivery vehicles.
Diffraction-limited optical microscopy lacks the resolution to directly characterize nanoscale features of single nanoparticles. This paper describes how structural features of gold nanostars can be ...identified using differential interference contrast (DIC) microscopy. First, we established structure–property relationships between categories of nanoparticle shapes and DIC optical images and then validated the correlation with electrodynamic simulations and electron microscopy. We found that DIC image patterns of single nanostars could be differentiated between 2D and 3D geometries. DIC images were also used to distinguish asymmetric and 4-fold symmetric structures and track nanoparticle orientation. Finally, we demonstrated how this wide-field optical technique can be used for in situ characterization of single nanoparticles rotating at a glass–water interface.
Identifying patients at risk of a 30-day readmission can help providers design interventions, and provide targeted care to improve clinical effectiveness. This study developed a risk model to predict ...a 30-day inpatient hospital readmission for patients in Maine, across all payers, all diseases and all demographic groups.
Our objective was to develop a model to determine the risk for inpatient hospital readmission within 30 days post discharge. All patients within the Maine Health Information Exchange (HIE) system were included. The model was retrospectively developed on inpatient encounters between January 1, 2012 to December 31, 2012 from 24 randomly chosen hospitals, and then prospectively validated on inpatient encounters from January 1, 2013 to December 31, 2013 using all HIE patients.
A risk assessment tool partitioned the entire HIE population into subgroups that corresponded to probability of hospital readmission as determined by a corresponding positive predictive value (PPV). An overall model c-statistic of 0.72 was achieved. The total 30-day readmission rates in low (score of 0-30), intermediate (score of 30-70) and high (score of 70-100) risk groupings were 8.67%, 24.10% and 74.10%, respectively. A time to event analysis revealed the higher risk groups readmitted to a hospital earlier than the lower risk groups. Six high-risk patient subgroup patterns were revealed through unsupervised clustering. Our model was successfully integrated into the statewide HIE to identify patient readmission risk upon admission and daily during hospitalization or for 30 days subsequently, providing daily risk score updates.
The risk model was validated as an effective tool for predicting 30-day readmissions for patients across all payer, disease and demographic groups within the Maine HIE. Exposing the key clinical, demographic and utilization profiles driving each patient's risk of readmission score may be useful to providers in developing individualized post discharge care plans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Among patients who are discharged from the Emergency Department (ED), about 3% return within 30 days. Revisits can be related to the nature of the disease, medical errors, and/or inadequate diagnoses ...and treatment during their initial ED visit. Identification of high-risk patient population can help device new strategies for improved ED care with reduced ED utilization.
A decision tree based model with discriminant Electronic Medical Record (EMR) features was developed and validated, estimating patient ED 30 day revisit risk. A retrospective cohort of 293,461 ED encounters from HealthInfoNet (HIN), Maine's Health Information Exchange (HIE), between January 1, 2012 and December 31, 2012, was assembled with the associated patients' demographic information and one-year clinical histories before the discharge date as the inputs. To validate, a prospective cohort of 193,886 encounters between January 1, 2013 and June 30, 2013 was constructed. The c-statistics for the retrospective and prospective predictions were 0.710 and 0.704 respectively. Clinical resource utilization, including ED use, was analyzed as a function of the ED risk score. Cluster analysis of high-risk patients identified discrete sub-populations with distinctive demographic, clinical and resource utilization patterns.
Our ED 30-day revisit model was prospectively validated on the Maine State HIN secure statewide data system. Future integration of our ED predictive analytics into the ED care work flow may lead to increased opportunities for targeted care intervention to reduce ED resource burden and overall healthcare expense, and improve outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gold nanostars functionalized with Gd(III) have shown significant promise as contrast agents for magnetic resonance imaging (MRI) because of their anisotropic, branched shape. However, the size and ...shape polydispersity of as-synthesized gold nanostars have precluded efforts to develop a rigorous relationship between the gold nanostar structure (e.g., number of branches) and relaxivity of surface-bound Gd(III). This paper describes the use of a centrifugal separation method that can produce structurally refined populations of gold nanostars and is compatible with Gd(III) functionalization. Combined transmission electron microscopy and relaxivity analyses revealed that the increased number of nanostar branches was correlated with enhanced relaxivity. By identifying the underlying relaxivity mechanisms for Gd(III)-functionalized gold nanostars, we can inform the design of high-performance MRI contrast agents.
Type 2 diabetes mellitus (T2DM), with increased risk of serious long-term complications, currently represents 8.3% of the adult population. We hypothesized that a critical transition state prior to ...the new onset T2DM can be revealed through the longitudinal electronic medical record (EMR) analysis.
We applied the transition-based network entropy methodology which previously identified a dynamic driver network (DDN) underlying the critical T2DM transition at the tissue molecular biological level. To profile pre-disease phenotypical changes that indicated a critical transition state, a cohort of 7,334 patients was assembled from the Maine State Health Information Exchange (HIE). These patients all had their first confirmative diagnosis of T2DM between January 1, 2013 and June 30, 2013. The cohort's EMRs from the 24 months preceding their date of first T2DM diagnosis were extracted.
Analysis of these patients' pre-disease clinical history identified a dynamic driver network (DDN) and an associated critical transition state six months prior to their first confirmative T2DM state.
This 6-month window before the disease state provides an early warning of the impending T2DM, warranting an opportunity to apply proactive interventions to prevent or delay the new onset of T2DM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Introduction ‘Transition’ not only involves finding an adult healthcare provider, but also includes the process of developing the patient’s ability to care for him/herself. Recent literature ...states that 40% of young adults with special healthcare needs are receiving the tools needed for transition. Pediatric urologists treating patients with complex anomalies, such as spina bifida, often anticipate poor outcomes for patients who are ill equipped for transition to adult care. The goal of this study was to identify potential barriers for young adults with neurogenic bladder when transitioning to independent care. Study design A prospective IRB-approved study was performed on all patients with neurogenic bladder referred to the transitional urology clinic. Reasons for missed appointments were tracked, and all patients were asked to complete the Transition Readiness Assessment Questionnaire (TRAQ) in private prior to an appointment. The TRAQ responses are scaled 1-5, with higher numbers corresponding to higher transition readiness of each individual skill. The mean score for each question was calculated across all patients, and the mean TRAQ score was calculated across all questions for each patient. To assess if certain subgroups were more prepared for transition, mean scores were compared between sexes, patients aged <19 and ≥19 years old, and between ambulatory and full-time wheelchair users with unpaired t -tests. Results A total of 73% (58/79) of patients referred to the transitional clinic came to their appointment. The most common reason for missed clinic appointments was related to health insurance coverage (47%). A total of 42 patients completed the TRAQ at a mean age of 19.5 years old; 90% (38/42) had spina bifida. Females, ambulatory patients, and those ≥19 years old had higher overall mean TRAQ scores, but these differences were not statistically significant. The highest TRAQ scores were related to taking and ordering medications, utilization of medical supplies, communication with healthcare providers, and assisting with household duties. The majority of the patients indicated ‘I am learning to do this’ ( Table 1 ). The lowest scores were in response to questions about health insurance coverage, payments for medications or medical equipment, financial help, and utilization of community services. Most patients responded ‘I do not know how but I want to learn’ ( Table 1 ). Conclusions Young adults with neurogenic bladder needed the most guidance during transition to independent care, with management of health insurance and finances. Based on these findings, dedicated social work and nurse visits have been included into the transition process.
Chronic pain and obesity are topics of increasing concern. When both diagnoses are present in the same patient, treatment can be complicated. This is a retrospective case-study looking at outcomes ...across the continuum of care for a patient with Grade III Obesity and chronic widespread pain. The patient completed a Pain Rehabilitation Center program. Progression was realised by following a deliberate, daily regimen, allowing for consistent activity despite the presence of significant physical symptoms and emotional distress.
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