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Amit K Singh,1,2 Megan A Hahn,2 Luke G Gutwein,3 Michael C Rule,4 Jacquelyn A Knapik,5 Brij M Moudgil,1,2 Stephen R Grobmyer,3 Scott C Brown,2,61Department of Materials Science and Engineering, College of Engineering, 2Particle Engineering Research Center, College of Engineering, 3Division of Surgical Oncology, Department of Surgery, College of Medicine, 4Cell and Tissue Analysis Core, McKnight Brain Institute, 5Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; 6DuPont Central Research and Development, Corporate Center for Analytical Science, Wilmington, DE, USABackground: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology.Methods: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model.Results: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis.Conclusion: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.Keywords: bioluminescence, in vivo imaging, mesoporous silica nanoparticles, NIR fluorescence, photothermal ablation, theranostic

Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR) light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs) after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs) for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm) retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026) in experimental tumor-bearing mice compared to control treated tumor-bearing mice.Conclusion: Fractionated photothermal therapy for cancer represents a new therapeutic paradigm enabled by the application of novel functional nanomaterials. MDT-NPs may advance clinical treatment of cancer by enabling fractionated real-time image guided photothermal therapy.Keywords: fluorescence, mesoporous silica, biodistribution, photothermal ablation, live animal imaging, near-infrared nanoparticle, breast cancer

Purpose. This article comments on the paper by Rene Jahiel and Marcia Joslyn Scherer elsewhere in this issue. Methods. This article adds theoretical constructs. Results. In commenting on their paper, this article makes four broad points. First, the sub-components identified by Drs. Jahiel and Scherer comprise critical factors of disability and the environment that must be taken into account when examining personal interactions with the environment. Second, as important as these factors are, operationalization of the model is hindered by a lack of mutual exclusivity between the sub-components both within and between the disability and environmental components. Third, power can be assessed in terms of the relative strength of individual functioning versus environmental functioning via a systematic appraisal of those elements essential to understanding the concept of accessibility. Finally, the demographic distinction between cohort and period trend analysis is an important consideration to take into account when assessing the time dimension, as the authors urge. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia (IDA) remains prevalent in Australia and worldwide, especially among high-risk groups. IDA may be effectively diagnosed in most cases by full blood examination and serum ferritin level. Serum iron levels should not be used to diagnose iron deficiency. Although iron deficiency may be due to physiological demands in growing children, adolescents and pregnant women, the underlying cause(s) should be sought. Patients without a clear physiological explanation for iron deficiency (especially men and postmenopausal women) should be evaluated by gastroscopy/colonoscopy to exclude a source of gastrointestinal bleeding, particularly a malignant lesion. Patients with IDA should be assessed for coeliac disease. Oral iron therapy, in appropriate doses and for a sufficient duration, is an effective first-line strategy for most patients. In selected patients for whom intravenous (IV) iron therapy is indicated, current formulations can be safely administered in outpatient treatment centres and are relatively inexpensive. Red cell transfusion is inappropriate therapy for IDA unless an immediate increase in oxygen delivery is required, such as when the patient is experiencing end-organ compromise (eg, angina pectoris or cardiac failure), or IDA is complicated by serious, acute ongoing bleeding. Consensus methods for administration of available IV iron products are needed to improve the utilisation of these formulations in Australia and reduce inappropriate transfusion. New-generation IV products, supported by high-quality evidence of safety and efficacy, may facilitate rapid administration of higher doses of iron, and may make it easier to integrate IV iron replacement into routine care. [ABSTRACT FROM AUTHOR]

Abstract:There is a lack of data on the dietary patterns and food preferences of African American women attending historically Black colleges and universities (HBCUs). African American women have higher death rates from cardiovascular disease than White women, and the initiating events of cardiovascular disease often begin in young adulthood. The purpose of this study was to identify the dietary patterns and food preferences of African American college women, which may act as risk factors for cardiovascular disease. A convenience sample of 100 African American women, ages 18 to 40 years, was administered two surveys assessing food preferences and dietary patterns. The majority of the participants (65%) preferred high-fat foods, and most of the participants (87%) consumed more than 30% of their daily caloric intake from fat. There is a definite need for dietary education regarding the impact of dietary fat on cardiovascular health among college students. [ABSTRACT FROM AUTHOR]

Researchers are gaining an interest in the concept of wisdom, a more holistic yet often ineffable educational outcome. Models of wisdom abound, but few have rigorously tested measures. This study looks at Brown's (2004a, 2004b) Model of Wisdom Development and its associated measure, the Wisdom Development Scale (WDS; Brown & Greene, 2006). The construct validity, measurement invariance, criterion validity, and reliability of scores from the WDS were assessed with over 3000 participants from two separate groups: one a sample of professionals and the other a sample of college students. Support for construct validity and reliability with these samples was found, along with measurement invariance. Latent means analyses showed predicted discrimination between the groups, and criterion validity evidence, with another measure of collegiate educational outcomes, was found. [ABSTRACT FROM AUTHOR]

An adult patient presented with an anomalous right pulmonary artery arising from the ascending aorta with severe unilateral pulmonary vascular disease of the left lung due to a large left-sided patent ductus arteriosus. A stenosis in the right pulmonary artery protected the right pulmonary vasculature. Right ventricular pressure was suprasystemic. After ductal ligation and surgical repair, pulmonary artery pressures fell dramatically. An immediate postoperative angiography confirmed extremely poor perfusion of the left lung. At four-and-a-half years of follow-up, the patient's quality of life had improved dramatically, main pulmonary artery pressure was one-sixth of systemic pressures, and there was vastly improved perfusion of the left lung at this lower perfusion pressure. The calculated pulmonary vascular resistance of the left lung was within normal limits. These findings suggested a significant degree of reversal of pulmonary hypertensive disease in the left lung sustained to 54 months postoperatively. [ABSTRACT FROM AUTHOR]

BACKGROUND: Research on contextual and neighborhood effects increasingly includes the built (physical) environment's influences on health and social well-being. A population-based study examined whether architectural features of the built environment theorized to promote observations and social interactions (e.g., porches, windows) predict Hispanic elders' psychological distress. METHODS: Coding of built environment features of all 3,857 lots across 403 blocks in East Little Havana, Florida, and enumeration of elders in 16,000 households was followed by assessments of perceived social support and psychological distress in a representative sample of 273 low socioeconomic status (SES) Hispanic elders. Structural-equation modeling was used to assess relationships between block-level built environment features, elders' perceived social support, and psychological distress. RESULTS: Architectural features of the front entrance such as porches that promote visibility from a building's exterior were positively associated with perceived social support. In contrast, architectural features such as window areas that promote visibility from a building's interior were negatively associated with perceived social support. Perceived social support in turn was associated with reduced psychological distress after controlling for demographics. Additionally, perceived social support mediated the relationship of built environment variables to psychological distress. CONCLUSIONS: Architectural features that facilitate direct, in-person interactions may be beneficial for Hispanic elders' mental health. [ABSTRACT FROM AUTHOR]

Mutations in fukutin related protein (FKRP) are responsible for a common group of muscular dystrophies ranging from adult onset limb girdle muscular dystrophies to severe congenital forms with associated structural brain involvement, including Muscle Eye Brain disease. A common feature of these disorders is the variable reduction in the glycosylation of skeletal muscle alpha-dystroglycan. In order to gain insight into the pathogenesis and clinical variability, we have generated two lines of mice, the first containing a missense mutation and a neomycin cassette, FKRP-Neo(Tyr307Asn) and the second containing the FKRP(Tyr307Asn) mutation alone. We have previously associated this missense mutation with a severe muscle-eye-brain phenotype in several families. Homozygote Fkrp-Neo(Tyr307Asn) mice die soon after birth and show a reduction in the laminin-binding epitope of alpha-dystroglycan in muscle, eye and brain, and have reduced levels of FKRP transcript. Homozygous Fkrp(Tyr307Asn) mice showed no discernible phenotype up to 6 months of age, contrary to the severe clinical course observed in patients with the same mutation. These results suggest the generation of a mouse model for FKRP related muscular dystrophy requires a knock-down rather than a knock-in strategy in order to give rise to a disease phenotype. [ABSTRACT FROM AUTHOR]

This study documents a 35% prevalence of clinically relevant depressive symptoms in a population-based sample of mostly Cuban older adults residing in a low-income, urban Miami neighborhood. This rate is comparable to, or higher than, prevalence rates reported by most other population-based samples of U.S. older adults. Logistic regression analyses indicate that perceived financial strain was the only sociodemographic factor associated with greater odds of clinically relevant symptoms when other sociodemographic factors were statistically controlled. Gender, age, and marital status were not related to elevated depressive symptoms. A case study illustrates the impact of financial strain on older adults' mental health. Findings highlight the need for mental health screening and case management services among these older adults, particularly those who experience financial strain. [ABSTRACT FROM AUTHOR]

Background and Purpose: The Personal Wellness Profile (PWP) is a 75-item questionnaire used to assess an individual's level of wellness in clinical and non-clinical settings. Currently, there are no published scientific data regarding the validity and reliability of the PWP. Therefore, this study was designed to assess convergence validity of the PWP using established instruments in which validity has been previously supported and to determine the reliability of the PWP using the test-retest method. Methods: A correlational design was used with a non-probability convenience sample of 100 African American women, ages 18 to 40 years, enrolled in a university in southern Louisiana. Convergence validity of the PWP was assessed by using the Michigan Alcoholism Screening Test (MAST), Drug Abuse Screening Test (DAST), Geisel man Food Preference Questionnaire II (GFPQ II), Weekly Stress Inventory (WSI), Fagerstrom Test for Nicotine Dependence (FTND), and the 7-Day Physical Activity Recall Questionnaire (PAR) as criteria. Results: The PWP had statistically significant correlations with two of the six subscales of the GFPQ II, and with the WSI, MAST, and FNTD. Findings also suggest that the PWP has moderate to moderately high internal consistency as a whole (r=.77), and that the subscale scores were also reliable over time (r=.52 to .90). Conclusions: The PWP will be valuable as a valid, standardized, highly portable tool that can be taken into the community and administered to African-Americans and other populations who do not readily have access to treatment, research and health care centers. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the effect of race on whether or not a patient would accept an invasive cardiac procedure when referred by a physician. Methods: A retrospective longitudinal review of medical records at a public health hospital in southeastern Louisiana was conducted to determine cardiovascular patient acceptance! rejection differences. Patient charts were examined using specific indicators (type of pain, laboratory values, blood pressure, and radiographic tests) to determine which patients were eligible to be referred. In order to be selected, each medical record had to have documentation of a physician referral for an invasive cardiac procedure. Medical charts without this referral were deemed ineligible for the cohort. Results: Patient preferences were similar for both minorities and Caucasians, despite the fact that the study controlled for disease severity, age, income, sex, race, social support, diagnosis, and family history. Conclusion: Race did not contribute to disparate acceptance and rejection rates among African Americans and Caucasians. A possible reason for this occurrence is that the site was a teaching hospital, which may indicate more physician oversight and better articulation of treatment options. Future studies should delve deeper into physician and institutional bias in non-teaching facilities during patient/physician interactions. [ABSTRACT FROM AUTHOR]

Muscular dystrophies with reduced glycosylation of alpha-dystroglycan (alpha-DG), commonly referred to as dystroglycanopathies, are a heterogeneous group of autosomal recessive conditions which include a wide spectrum of clinical severity. Reported phenotypes range from severe congenital onset Walker-Warburg syndrome (WWS) with severe structural brain and eye involvement, to relatively mild adult onset limb girdle muscular dystrophy (LGMD). Specific clinical syndromes were originally described in association with mutations in any one of six demonstrated or putative glycosyltransferases. Work performed on patients with mutations in the FKRP gene has identified that the spectrum of phenotypes due to mutations in this gene is much wider than originally assumed. To further define the mutation frequency and phenotypes associated with mutations in the other five genes, we studied a large cohort of patients with evidence of a dystroglycanopathy. Exclusion of mutations in FKRP was a prerequisite for participation in this study. Ninety-two probands were screened for mutations in POMT1, POMT2, POMGnT1, fukutin and LARGE. Homozygous and compound heterozygous mutations were detected in a total of 31 probands (34 individuals from 31 families); 37 different mutations were identified, of which 32 were novel. Mutations in POMT2 were the most prevalent in our cohort with nine cases, followed by POMT1 with eight cases, POMGnT1 with seven cases, fukutin with six cases and LARGE with only a single case. All patients with POMT1 and POMT2 mutations had evidence of either structural or functional central nervous system involvement including four patients with mental retardation and a LGMD phenotype. In contrast mutations in fukutin and POMGnT1 were detected in four patients with LGMD and no evidence of brain involvement. The majority of patients (six out of nine) with mutations in POMT2 had a Muscle-Eye-Brain (MEB)-like condition. In addition we identified a mutation in the gene LARGE in a patient with WWS. Our data expands the clinical phenotypes associated with POMT1, POMT2, POMGnT1, fukutin and LARGE mutations. Mutations in these five glycosyltransferase genes were detected in 34% of patients indicating that, after the exclusion of FKRP, the majority of patients with a dystroglycanopathy harbour mutations in novel genes. [ABSTRACT FROM AUTHOR]

Objective To identify physiological and psychosocial variables of young African American women that may serve as a risk factor for heart disease and to assess their health promotion programme preferences. Method A descriptive design was used to assess the cardiovascular risk factors of 100 African American women ages 18 to 40 years, enrolled in a Historically Black College and University (HBCU) in the south. The instruments included four questionnaires: a demographic questionnaire, Gieselman Food Preference Questionnaire (GFPQ), PBRC Food Frequency Questionnaire (FFQ), and the Personal Wellness Profile (PWP). Physiological data were obtained using a stadiometer, beam balance scale, Lifescan Blood Glucose Monitoring System, BioScanner 2000 Test System, sphygmomanometer, and carbon monoxide analyser.Results The mean age of the participants was 25.5 (SD=5.8) years. The overall PWP wellness score for the participants was 43 (SD=15) with a range from 10 to 74. Of the 100 participants, 55 per cent had increased body mass index (BMI); 66 per cent had increased waist-to-hip ratios; 49 per cent 'did not' engage in an exercise programme, and 45 per cent consumed a diet that was 'mostly high' to 'high' in fat content. The majority of the participants (92 per cent) reported that they had a good social support system. Fifty-five per cent of the women reported an interest in the following health promotion programmes: weight management, nutrition, aerobics, and women's health.Conclusion Information obtained from this study can be useful in developing culturally-customised, gender-appropriate, interventions for this select population of women. Early interventions with young African American women that focus on diet, exercise and weight management may reduce the risk and incidence of cardiovascular disease. The college years is considered a time for adaptation, and as such, is an opportune time to educate individuals on health promoting behaviours and the long-term effect that health promoting behaviours can have on their lives. Research to gain new insights on factors that reduce cardiovascular risk behaviour in African American women is critical to advancing the health of African American women. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate racial and gender differences in the utilization of invasive procedures for cardiovascular treatment. Medical records data of 3015 patients were abstracted from a Medical System Database from 1999 to 2001. Logit models were used to estimate the adjusted odds in the utilization, referral, and acceptance of invasive procedures, while controllingfor confounders (age, race, sex, comorbidity, disease severity, payer type, marital status and family history) simultaneously. When considering utilization of invasive procedures, the adjusted odds were lower for African-Americans compared to Caucasians. There was a statistically significant difference (p < .05) in Coronary Artery Bypass Graft (CABG) utilization between African Americans and Caucasians. African Americans were less likely than Caucasians to receive a CABG. Although not statistically significant, African-Americans were less likely than Caucasians to receive a cardiac catheterization and Percutaneous Transluminal Coronary Angioplasty (PTCA). Findings failed to yield a statistical significance for gender disparities regarding invasive procedure utilizations. [ABSTRACT FROM AUTHOR]

Husbands and wives experience role changes when they become caregivers for their spouses disabled due to stroke. This pilot study examined the feelings and beliefs of these primary caregivers. Caregivers reported a high degree of dislike for the traditional marital role responsibilities of the opposite gender spouse. Nurses can use anticipatory guidance and other strategies to prepare caregivers and assist them in their new roles. [ABSTRACT FROM AUTHOR]

The article offers information on a study that was conducted to determine the outcome of pulmonary artery banding (PAB) in an open-ended strategy for systemic right ventricles (RV). The results revealed that the PAB can be performed with no mortality and low morbidity. PAB in such patients provides true open ended palliation by allowing left ventricular training in those going for anatomical repair, stabilizing or improving RV function thereby delaying surgery.

Abstract The 4th High Level Forum on Aid Effectiveness, held in Busan, South Korea in November 2011 again promised an opportunity for a "new consensus on development cooperation" to emerge. This paper reviews the recent evolution of the concept of coordination for development assistance in health as the basis from which to understand current discourses. The paper reviews peer-reviewed scientific literature and relevant 'grey' literature, revisiting landmark publications and influential authors, examining the transitions in the conceptualisation of coordination, and the related changes in development assistance. Four distinct transitions in the understanding, orientation and application of coordination have been identified: coordination within the sector, involving geographical zoning, sub-sector specialisation, donor consortia, project co-financing, sector aid, harmonisation of procedures, ear-marked budgetary support, donor agency reform and inter-agency intelligence gathering; sector-wide coordination, expressed particularly through the Sector-Wide Approach; coordination across sectors at national level, expressed in the evolution of Poverty Strategy Reduction Papers and the national monitoring of the Millennium Development Goals; and, most recently, global-level coordination, embodied in the Paris Principles, and the emergence of agencies such as the International Health Partnerships Plus. The transitions are largely but not strictly chronological, and each draws on earlier elements, in ways that are redefined in the new context. With the increasing complexity of both the territory of global health and its governance, and increasing stakeholders and networks, current imaginings of coordination are again being challenged. The High Level Forum in Busan may have been successful in recognising a much more complex landscape for development than previously conceived, but the challenges to coordination remain.

Abstract Background Interleukin-4 (IL4) is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths 1. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. Results This analysis revealed evidence of diversifying selection at 15 residues, clustered in epitopes responsible for IL4 binding to its Type I and Type II receptors. Such a striking signature of selective pressure suggested either recurrent episodes of pathogen antagonism or ligand/receptor co-evolution. To test the latter possibility, we performed detailed functional analysis of IL4 allotypes expressed by Mus musculus musculus and Mus musculus castaneus, which happen to differ at 5 residues (including three at positively selected sites) in and adjacent to the site 1 epitope that binds the IL4Rα subunit shared by the Type I and Type II IL4 receptors. We show that this intra-species variation affects the ability of IL4 neither to bind IL4 receptor alpha (IL4Rα) nor to signal biological responses through its Type I receptor. Conclusions Our results -- reminiscent of clustered positively selected sites revealing functionally important residues at host-virus interaction interfaces -- are consistent with IL4 having evolved to avoid recurrent pathogen antagonism, while maintaining the capacity to bind and signal through its cognate receptor. This work exposes what may be a general feature of evolutionary conflicts fought by pathogen antagonists at host protein-protein interaction interfaces involved in immune signaling: the emergence of receptor-binding ligand epitopes capable of buffering amino acid variation.