Oligonucleotide-Functionalized Gold Nanoparticles for Synchronous Telomerase Inhibition, Radiosensitization, and Delivery of Theranostic Radionuclides

Telomerase represents an attractive target in oncology as it is expressed in cancer but not in normal tissues. The oligonucleotide inhibitors of telomerase represent a promising anticancer strategy, although poor cellular uptake can restrict their efficacy. In this study, gold nanoparticles (AuNPs) were used to enhance oligonucleotide uptake. “match” oligonucleotides complementary to the telomerase RNA template subunit (hTR) and “scramble” (control) oligonucleotides were conjugated to diethylenetriamine pentaacetate (DTPA) for 111In-labeling. AuNPs (15.5 nm) were decorated with a monofunctional layer of oligonucleotides (ON–AuNP) or a multifunctional layer of oligonucleotides, PEG(polethylene glycol)800-SH (to reduce AuNP aggregation) and the cell-penetrating peptide Tat (ON–AuNP–Tat). Match–AuNP enhanced the cellular uptake of radiolabeled oligonucleotides while retaining the ability to inhibit telomerase activity. The addition of Tat to AuNPs increased nuclear localization. 111In–Match–AuNP–Tat induced DNA double-strand breaks and caused a dose-dependent reduction in clonogenic survival of telomerase-positive cells but not telomerase-negative cells. hTR inhibition has been reported to sensitize cancer cells to ionizing radiation, and 111In–Match–AuNP–Tat therefore holds promise as a vector for delivery of radionuclides into cancer cells while simultaneously sensitizing them to the effects of the emitted radiation

Decision Support Intervention for people with advanced dementia residing in a nursing home: A study protocol for an International advance care planning intervention (mySupport study)

Background Where it has been determined that a resident in a nursing home living with dementia loses decisional capacity, nursing home staff must deliver care that is in the person's best interests. Ideally, decisions should be made involving those close to the person, typically a family carer and health and social care providers. The aim of the Family Carer Decisional Support intervention is to inform family carers on end-of-life care options for a person living with advanced dementia and enable them to contribute to advance care planning. This implementation study proposes to; 1) adopt and apply the intervention internationally; and, 2) train nursing home staff to deliver the family carer decision support intervention. Methods This study will employ a multiple case study design to allow an understanding of the implementation process and to identify the factors which determine how well the intervention will work as intended. We will enrol nursing homes from each country (Canada n = 2 Republic of Ireland = 2, three regions in the UK n = 2 each, The Netherlands n = 2, Italy n = 2 and the Czech Republic n = 2) to reflect the range of characteristics in each national and local context. The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework will guide the evaluation of implementation of the training and information resources. Our mixed methods study design has three phases to (1) establish knowledge about the context of implementation, (2) participant baseline information and measures and (3) follow up evaluation. Discussion The use of a multiple case study design will enable evaluation of the intervention in different national, regional, cultural, clinical, social and organisational contexts, and we anticipate collecting rich and in-depth data. While it is hoped that the intervention resources will impact on policy and practice in the nursing homes that are recruited to the study, the development of implementation guidelines will ensure impact on wider national policy and practice. It is our aim that the resources will be sustainable beyond the duration of the study and this will enable the resources to have a longstanding relevance for future advance care planning practice for staff, family carers and residents with advanced dementia

Implementation of nutritional guidelines in a university hospital monitored by repeated point prevalence surveys

Background/Objectives: Malnutrition is present in 20–50% of hospitalized patients, and nutritional care is a challenge. The aim was to evaluate whether the implementation of a nutritional strategy would influence nutritional care performance in a university hospital. Subjects/Methods: This was a prospective quality improvement program implementing guidelines for nutritional care, with the aim of improving nutritional practice. The Nutrition Risk Screening (NRS) 2002 was used. Point prevalence surveys over 2 years to determine whether nutritional practice had improved. Results: In total, 3604 (70%) of 5183 eligible patients were screened and 1230 (34%) were at nutritional risk. Only 53% of the at-risk patients got nutritional treatment and 5% were seen by a dietician. The proportion of patients screened increased from the first to the eighth point prevalence survey (P=0.012), but not the proportion of patients treated (P=0.66). The four initial screening questions in NRS 2002 identified 92% of the patients not at nutritional risk. Conclusions: Implementation of nutritional guidelines improved the screening performance, but did not increase the proportion of patients who received nutritional treatment. Point prevalence surveys were useful to evaluate nutritional practice in this university hospital. In order to improve practice, we suggest using only the four initial screening questions in NRS 2002 to identify patients not at risk, better education in nutritional care for physicians and nurses, and more dieticians employed. Audit of implementation of guidelines, performed by health authorities, and specific reimbursement for managing nutrition may also improve practice.publishedVersio

Assessment of left ventricular volumes; reliable by gated SPECT?

Ventricular Dysfunction & Heart Failur

Assessment of left ventricular function: visual or quantitative?

Cardiovascular Aspects of Radiolog

The impact of the mySupport advance care planning intervention on family caregivers' perceptions of decision-making and care for nursing home residents with dementia: pretest-posttest study in six countries

Background the mySupport advance care planning intervention was originally developed and evaluated in Northern Ireland (UK). Family caregivers of nursing home residents with dementia received an educational booklet and a family care conference with a trained facilitator to discuss their relative's future care. Objectives to investigate whether upscaling the intervention adapted to local context and complemented by a question prompt list impacts family caregivers' uncertainty in decision-making and their satisfaction with care across six countries. Second, to investigate whether mySupport affects residents' hospitalisations and documented advance decisions. Design a pretest-posttest design. Setting in Canada, the Czech Republic, Ireland, Italy, the Netherlands and the UK, two nursing homes participated. Participants in total, 88 family caregivers completed baseline, intervention and follow-up assessments. Methods family caregivers' scores on the Decisional Conflict Scale and Family Perceptions of Care Scale before and after the intervention were compared with linear mixed models. The number of documented advance decisions and residents' hospitalisations was obtained via chart review or reported by nursing home staff and compared between baseline and follow-up with McNemar tests. Results family caregivers reported less decision-making uncertainty (-9.6, 95% confidence interval: -13.3, -6.0, P < 0.001) and more positive perceptions of care (+11.4, 95% confidence interval: 7.8, 15.0; P < 0.001) after the intervention. The number of advance decisions to refuse treatment was significantly higher after the intervention (21 vs 16); the number of other advance decisions or hospitalisations was unchanged. Conclusions the mySupport intervention may be impactful in countries beyond the original setting.Public Health and primary careGeriatrics in primary car

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Cardiac Dysfunction and Arrhythmia

Use of the anterior-posterior chest diameter in CT: reduction in radiation dose?

Vascular Biology and Interventio

Increased accuracy in computed tomography coronary angiography; a new body surface area adapted protocol

Vascular Biology and Interventio

Left ventricular mass assessment by CMR; how to define the optimal index

Vascular Biology and Interventio