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Gold nanoparticles stabilized with MPEG-grafted poly(l-lysine): in vitro and in vivo evaluation of a potential theranostic agent

Fri, 07/22/2016 - 1:58pm

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 ± 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were stable against aggregation in the presence of phosphate and serum proteins and remained dispersed after their uptake into endosomes. MPEG-gPLL-stabilized AuNP3 exhibited high uptake and very low toxicity in human endothelial cells, but showed a high dose-dependent toxicity in epithelioid cancer cells. Highly stable radioactive labeling of AuNP3 with (99m)Tc allowed imaging of AuNP3 biodistribution and revealed dose-dependent long circulation in the blood. The minor fraction of AuGNP3 was found in major organs and at sites of experimentally induced inflammation. Gold analysis showed evidence of a partial degradation of the MPEG-gPLL layer in AuNP3 particles accumulated in major organs. Radiofrequency-mediated heating of AuNP3 solutions showed that AuNP3 exhibited heating behavior consistent with 10 nm core nanoparticles. We conclude that PEG-pPLL coating of AuNPs confers "stealth" properties that enable these particles to exist in vivo in a nonaggregating, biocompatible state making them suitable for potential use in biomedical applications such as noninvasive radiofrequency cancer therapy.

Substrate-Based Near-Infrared Imaging Sensors Enable Fluorescence Lifetime Contrast via Built-in Dynamic Fluorescence Quenching Elements

Fri, 07/22/2016 - 1:57pm

Enzymatic activity sensing in fluorescence lifetime (FLT) mode with “self-quenched” macromolecular near-infrared (NIR) sensors is a highly promising strategy for in vivo imaging of proteolysis. However, the mechanisms of FLT changes in such substrate-based NIR sensors have not yet been studied. We synthesized two types of sensors by linking the near-infrared fluorophore IRDye 800CW to macromolecular graft copolymers of methoxy polyethylene glycol and polylysine (MPEG-gPLL) with varying degrees of MPEGylation and studied their fragmentation induced by trypsin, elastase, plasmin, and cathepsins (B,S,L,K). We determined that the efficiency of such NIR sensors in FLT mode depends on sensor composition. While MPEG-gPLL with a high degree of MPEGylation showed rapid (τ1/2 = 0.1–0.2 min) FLT increase (Δτ = 0.25 ns) upon model proteinase-mediated hydrolysis in vivo, lower MPEGylation density resulted in no such FLT increase. Temperature-dependence of fluorescence dequenching of NIR sensors pointed to a mixed dynamic/static-quenching mode of MPEG-gPLL-linked fluorophores. We further demonstrated that although the bulk of sensor-linked fluorophores were dequenched due to the elimination of static quenching, proteolysis-mediated deletion of a fraction of short (8–10 kD) negatively charged fragments of highly MPEGylated NIR sensor is the most likely event leading to a rapid FLT increase phenomenon in quenched NIR sensors. Therefore, the optimization of “built-in” dynamic quenching elements of macromolecular NIR sensors is a potential avenue for improving their response in FLT mode.

Tweet, Like, Share: Using Social Media to Connect with the Evaluation World

Fri, 07/22/2016 - 12:23pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Searching for Literature Using Google Scholar

Thu, 07/21/2016 - 8:53pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Driving Change: Tips for Helping Stakeholders Stay Motivated

Thu, 07/21/2016 - 8:53pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

The Beauty of Banner Tables

Thu, 07/21/2016 - 8:53pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

What explains the link between reproductive events and women's longevity

Wed, 07/20/2016 - 9:52am

Introduction: Several investigations have shown a link between older age at last birth and extreme longevity. The latest study in the current issue of Menopause found that women giving birth to their last child beyond age 33 years had twice the odds of being in the top 5% of survival. Consistent with these results, age at final menstrual period (FMP) also has been shown to predict subsequent mortality, with lower mortality in women with older age at FMP. FMP results from a loss of ovarian follicles, which presumably also affects age at last birth. Of the few studies investigating the relationship between age at last birth and age at FMP, several —though not all —have indicated a positive association. Thus, a similar set of factors may explain the link between age at last birth and longevity and the link between age at FMP and subsequent morbidity/mortality.

Evaluation of tobacco use on Chinese population through ATTOC model: a cross-sectional survey on hospitalized psychiatric patients

Wed, 07/20/2016 - 9:51am

OBJECTIVES: To evaluate the feasibility of Addressing Tobaccos through Organizational Change (ATTOC) intervention to Chinese psychiatric patients, and to better address tobacco use through the ATTOC intervention model in the context of China.

METHODS: The study was conducted in Mental Health Center of West China Hospital in 2010. A total of 100 hospitalized psychiatric patients were recruited to carry out ATTOC intervention. Subjects suffers from mental illness were diagnosed by professional psychiatrists according to the International Statistical Classification of Diseases (ICD-10) criteria.

RESULTS: The prevalence of tobacco use in hospitalized psychiatric patients were closely correlated with the type of mental illness, family smoking history, sex, age, marital status, education status, etc. However, most psychiatric patients knew little about these, and tended to ignore the importance of smoking cessation.

CONCLUSIONS: The ATTOC intervention program of the U.S. may be suitable for hospitalized Chinese psychiatric patients, and it could be applied for the tobacco smoking treatment in China. However, the health effects of tobacco use still did not draw amount attentions from both the clinicians and general public. It is urgently needed to raise people's awareness and carry out ATTOC intervention to control tobacco use, and ultimately terminate tobacco use.

Influence of race/ethnicity, body mass index, and proximity of menopause on menstrual cycle patterns in the menopausal transition: the Study of Women's Health Across the Nation

Wed, 07/20/2016 - 9:51am

OBJECTIVE: Few studies have evaluated factors that influence menstrual cycle length (MCL) during the menopausal transition (MT), a life stage during which very long cycles become more likely to occur. The objective of this article was to assess how body mass index and race/ethnicity--factors associated with MCL in young women--influence MCL during the MT.

METHODS: Study of Women's Health Across the Nation menstrual calendar substudy data of African-American, white, Chinese, and Japanese women were available for three sites (southeastern Michigan, Los Angeles, and northern California). Self-recorded monthly menstrual calendars with end-of-the-month questions on hormone therapy use and smoking were collected from 1996 to 2006. Height and weight were measured at annual study visits. We used quantile regression to model MCL at the 25th, 50th, 75th, and 90th percentiles with bootstrap sampling to construct 95% CIs. Models evaluated MCL with time indexed to the start of the MT (n = 963) and to the final menstrual period (n = 431).

RESULTS: During the MT, increases in MCL occurred mostly at the right tail of the distribution, reflecting a lengthening of long menstrual cycles, not of the median MCL. After adjustment for smoking, education, physical activity, and time, Chinese and Japanese women had 1 day to 6 days longer MCLs compared with white women. Obese women had 1 day to 5 days longer MCLs compared with nonobese women.

CONCLUSIONS: As occurs in younger women, menstrual characteristics during the MT are influenced by race/ethnicity and obesity. The long menstrual cycles characteristic of the MT are longer in obese women and in Chinese and Japanese women.

Parent preferences for telephone coaching to prevent and manage childhood obesity

Wed, 07/20/2016 - 9:51am

OBJECTIVE: To assess parent preferences for utilisation of a parent-focused, telephone-based coaching service, or 'FITLINE,' to prevent or manage childhood obesity.

METHODS: A cross-sectional survey of parents of children aged 2-12 years was conducted at a paediatric practice in Greater Boston, Massachusetts, USA, between July 2012 and May 2013. Parents received questionnaires with clinic visit paperwork and opted-in to the study by returning them to clinic staff or by mail. The anonymous pen-to-paper questionnaire assessed parents' potential FITLINE utilisation, preferences regarding educational content and logistics, and parent/child demographics. Simple logistical regression was used to assess associations between parent and child factors and FITLINE interest.

RESULTS: Among n=114 participants, most parents reported being very likely (n=53, 48%) or somewhat likely (n=44, 40%) to use a FITLINE-promoting healthy habits for children if it was made available. Interest in a FITLINE was greatest among overweight or obese parents (OR 3.12, CI 1.17 to 8.30) and those with children aged < 5 years (OR 2.42, CI 1.02 to 5.73). Parents desired to discuss their own health and fitness goals (84%) along with educational topics such as healthy food shopping on a budget (91%) and how to meet children's physical activity needs (81%). Most parents preferred to obtain a FITLINE referral from a paediatrician or nurse (73%), instead of a school nurse (42%) or child-care provider (26%).

CONCLUSIONS: Given strong interest among parents in a FITLINE and the urgency of the youth obesity epidemic, implementation of a pilot phone-based service should be strongly considered.

Duration of menopausal vasomotor symptoms over the menopause transition

Wed, 07/20/2016 - 9:51am

IMPORTANCE: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments.

OBJECTIVES: To determine total duration of frequent VMS ( > /= 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence.

DESIGN, SETTING, AND PARTICIPANTS: The Study of Women's Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS.

MAIN OUTCOMES AND MEASURES: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause.

RESULTS: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, > 11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS.

CONCLUSIONS AND RELEVANCE: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Impaired insight into delusions predicts treatment outcome during a randomized controlled trial for Psychotic Depression (STOP-PD study)

Wed, 07/20/2016 - 9:51am

BACKGROUND: Insight into delusional beliefs varies in patients with major depressive disorder (MDD) with psychotic features ("psychotic depression"). The relationship between impaired insight and illness severity and its impact on treatment outcomes has not been studied in psychotic depression. As such, the aim of this analysis was to explore the relationship among impaired insight, patient characteristics (ie, illness severity, cognition, suicidality, and social functioning), and treatment outcome (ie, remission) during acute treatment of psychotic depression.

METHOD: This secondary analysis is based on the data from the Study of Pharmacotherapy for Psychotic Depression (STOP-PD) in which 259 participants meeting DSM-IV criteria for MDD with psychotic features enrolled between December 2002 and June 2007 (including 142 aged > /= 60 years) in a 4-center, 12- week, double-blind, randomized controlled trial funded by the US National Institutes of Health. Insight into delusions was assessed using the Delusion Assessment Scale (DAS). The primary outcomes were the predictive utility of insight into illness (ie, Hamilton Depression Rating Scale [HDRS] insight item) and insight into delusions (conviction factor derived from the DAS) on final treatment outcome at 12 weeks of treatment (ie, full remission, partial remission, and nonremission).

RESULTS: At baseline, impaired insight into delusions was positively associated with illness severity (HDRS-16 which excluded the insight item, r = 0.15, P = .016) and negatively correlated with measures of cognition (P < .05). Improvement in insight was not associated with changes in cognition, suicidality, or social functioning after adjusting for covariates. Independent of the severity of depression or psychosis, impaired insight into delusions at baseline (chi(2) = 11.65, P = .020) and after 3 (chi(2) = 9.62, P = .047), 6 (chi(2) = 6.97, P = .031), and 8 (chi(2) = 9.08, P = .011) weeks of treatment predicted remission at the end of the trial.

CONCLUSIONS: Impaired insight into delusions appears to be an independent predictor of remission in MDD with psychotic features during acute treatment, suggesting that more attention should be paid to this symptom. Longitudinal studies are required to determine the impact of impaired insight into delusions on long-term outcomes, including relapse.

TRIAL REGISTRATION: identifier: NCT00056472.

Meaning in life in chronic pain patients over time: associations with pain experience and psychological well-being

Wed, 07/20/2016 - 9:51am

We explored the relationship between meaning in life and adjustment to chronic pain in a three-wave, 2 year, longitudinal study of 273 Belgian chronic pain patients. We examined the directionality of the relationships among the meaning in life dimensions (Presence of Meaning and Search for Meaning) and indicators of adjustment (depressive symptoms, life satisfaction, pain intensity, and pain medication use). We found that Presence of Meaning was an important predictor of well-being. Secondly, we used a typological methodology to distinguish meaning in life profiles, and the relationship of individual meaning in life profiles with indicators of adjustment. Five meaning in life profiles emerged: High Presence High Search, High Presence Low Search, Moderate Presence Moderate Search, Low Presence Low Search, and Low Presence High Search. Each meaning in life profile was associated with a unique adjustment outcome. Profiles that scored high on Presence of Meaning showed more optimal adjustment. The profiles showed little change over time and did not moderate the development of adjustment indicators, except for life satisfaction. Practical implications and suggestions for future research are discussed.

Effect of Different Meditation Types on Migraine Headache Medication Use

Wed, 07/20/2016 - 9:51am

Spiritual meditation has been found to reduce the frequency of migraines and physiological reactivity to stress. However, little is known about how introducing a spirituality component into a meditation intervention impacts analgesic medication usage. In this study, 92 meditation-naive participants were randomly assigned to one of four groups: (1) Spiritual Meditation, (n = 25), (2) Internally Focused Secular Meditation (n = 23), (3) Externally Focused Secular Meditation (n = 22), or (4) Progressive Muscle Relaxation (n = 22); and practiced their technique for 20 min/day over 30 days while completing daily diaries. Headache frequency, headache severity, and pain medication use were assessed. Migraine frequency decreased in the Spiritual Meditation group compared to other groups (p < 0.05). Headache severity ratings did not differ across groups (p = ns). After adjusting for headache frequency, migraine medication usage decreased in the Spiritual Meditation group compared to other groups (p < 0.05). Spiritual Meditation was found to not affect pain sensitivity, but it does improve pain tolerance with reduced headache related analgesic medication usage.

Accumulation of metabolic cardiovascular risk factors in black and white young adults over 20 years

Wed, 07/20/2016 - 9:50am

BACKGROUND: Cross-sectional clustering of metabolic risk factors for cardiovascular disease in middle-aged adults is well described, but less is known regarding the order in which risk factors develop through young adulthood and their relation to subclinical atherosclerosis.

METHOD AND RESULTS: A total of 3178 black and white women and men in the Coronary Artery Risk Development in Young Adults study were assessed to identify the order in which cardiovascular disease risk factors including diabetes, hypertension, dyslipidemia (low high-density lipoprotein cholesterol or high triglyceride levels), hypercholesterolemia (high total or low-density lipoprotein cholesterol), and obesity develop. Observed patterns of risk factor development were compared with those expected if risk factors accumulated randomly, given their overall distribution in the population. Over the 20 years of follow-up, 80% of participants developed at least 1 risk factor. The first factor to occur was dyslipidemia in 39% of participants, obesity in 20%, hypercholesterolemia in 11%, hypertension in 7%, and diabetes in 1%. Dyslipidemia was the only risk factor both to occur first and to be followed by additional risk factors more often than expected (P < 0.001 for both). Order of risk factor accrual did not affect subclinical atherosclerosis at year 20. Results were similar by sex, race, and smoking status.

CONCLUSIONS: Multiple patterns of cardiovascular risk factor development were observed from young adulthood to middle age. Dyslipidemia, a potentially modifiable condition, often preceded the development of other risk factors and may be a useful target for intervention and monitoring.

Food insecurity and health: data from the Veterans Aging Cohort Study

Wed, 07/20/2016 - 9:50am

OBJECTIVE: Food insecurity may be a modifiable and independent risk factor for worse control of medical conditions, but it has not been explored among veterans. We determined the prevalence of, and factors independently associated with, food insecurity among veterans in the Veterans Aging Cohort Study (VACS).

METHODS: Using data from VACS from 2002-2008, we determined the prevalence of food insecurity among veterans who have accessed health care in the Veterans Health Administration (VA) as defined by "concern about having enough food for you or your family in the past month." We used multivariable logistic regression to determine factors independently associated with food insecurity and tests of trend to measure the association between food insecurity and control of hypertension, diabetes, HIV, and depression.

RESULTS: Of the 6,709 veterans enrolled in VACS, 1,624 (24%) reported being food insecure. Food insecurity was independently associated with being African American, earning <$25,000/year, recent homelessness, marijuana use, and depression. Being food insecure was also associated with worse control of hypertension, diabetes, HIV, and depression (p < 0.001).

CONCLUSION: Food insecurity is prevalent and associated with worse control of medical conditions among veterans who have accessed care in the VA.

The association between patient activation and medication adherence, hospitalization, and emergency room utilization in patients with chronic illnesses: a systematic review

Wed, 07/20/2016 - 9:50am

OBJECTIVE: A systematic review of the published literature on the association between the PAM (Patient Activation Measure) and hospitalization, emergency room use, and medication adherence among chronically ill patient populations.

METHODS: A literature search of several electronic databases was performed. Studies published between January 1, 2004 and June 30, 2014 that used the PAM measure and examined at least one of the outcomes of interest among a chronically ill study population were identified and systematically assessed.

RESULTS: Ten studies met the eligibility criteria. Patients who scored in the lower PAM stages (Stages 1 and 2) were more likely to have been hospitalized. Patients who scored in the lowest stage were also more likely to utilize the emergency room. The relationship between PAM stage and medication adherence was inconclusive in this review.

CONCLUSION: Chronically ill patients reporting low stages of patient activation are at an increased risk for hospitalization and ER utilization.

PRACTICAL IMPLICATIONS: Future research is needed to further understand the relationship between patient activation and medication adherence, hospitalization and/or ER utilization in specific chronically ill (e.g. diabetic, asthmatic) populations. Research should also consider the role of patient activation in the development of effective interventions which seek to address the outcomes of interest.

Family income, parental education and brain structure in children and adolescents

Wed, 07/20/2016 - 9:50am

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.