Synthesis and aggregation of a porphyrin cored hyperbranched polyglycidol and its application as a macromolecular photosensitizer for photodynamic therapy.

Macromolecules are potentially useful delivery systems for cancer drugs as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protecting and solubilizing toxic and hydrophobic drug moieties. Overall these properties and abilities can result in an enhanced therapeutic effect. Photodynamic therapy (PDT) combines the use of oxygen and a photosensitizer (PS), that become toxic upon light-irradiation. We proposed that a PS encapsulated within a water-soluble macromolecule could exploit the EPR effect and safely and selectively deliver the PS to a tumor. In this paper, we describe the synthesis of a porphyrin cored hyperbranched polymer that aggregated into larger micellar structures. DLS and TEM indicated that these aggregated structures had diameters of 45 nm and 20 nm for the solvated and non-solvated species respectively. The porphyrin cored HBP (PC-HBP), along with the non-encapsulated porphyrin (THPP), were screened against EJ bladder carcinoma cells in the dark and light. Both THPP and PC-HBP displayed good toxicity in the light, with LD50 concentrations of 0.5 μM and 1.7 μM respectively. However, in the dark, the non-incorporated porphyrin (THPP) displayed significant toxicity, generating an LD50 of 4 μM. On the other hand, no dark toxicity was observed for the polymer system (PC-HBP) at concentrations of 100 μM or less. As such, incorporation within the large polymer aggregate serves to eliminate dark toxicity, whilst maintaining excellent toxicity when irradiated

Factors determining the integration of nutritional genomics into clinical practice by registered dietitians

YesPersonalized nutrition has the potential to improve health, prevent disease and reduce healthcare expenditure. Whilst research hints at positive consumer attitudes towards personalized nutrition that draws upon lifestyle, phenotypic and genotypic data, little is known about the degree to which registered dietitians (RD) are engaged in the delivery of such services. This review sought to determine possible factors associated with the integration of the emerging science of Nutritional Genomics (NGx) into the clinical practice setting by practicing registered dietitians. Scope Search of online databases (Pubmed; National Library of Medicine; Cochrane Library; Ovid Medline) was conducted on material published from January 2000 to December 2014. Studies that sampled practicing dietitians and investigated integration or application of NGx and genetics knowledge into practice were eligible. Articles were assessed according to the American Dietetic Association Quality Criteria Checklist. Key findings Application of nutritional genomics in practice has been limited. Reluctance to integrate NGx into practice is associated with low awareness of NGx, a lack of confidence in the science surrounding NGx and skepticism toward Direct to consumer (DTC) products. Successful application to practice was associated with knowledge about NGx, having confidence in the science, a positive attitude toward NGx, access to DTC products, a supportive working environment, working in the clinical setting rather than the public health domain and being in private rather than public practice. Conclusions There is a need to provide RGs with a supportive working environment that provides ongoing training in NGx and which is integrated with clinical practice

Perceptions and experiences of early-adopting registered dietitians in integrating nutrigenomics into practice

yesPurpose - This research explores the perceptions and experiences of early adopters of the technology. Design/Method/Approach - Registered Dietitians (RD´s) (N=14) were recruited from the UK, Canada, South-Africa, Australia, Mexico and Israel. Six qualitative interviews and two focus groups were conducted online using a conference calling platform. Data were recorded, transcribed and thematically analysed. Findings - Early adopters of Nutrigenomics (NGx) were experienced, self-efficacious RD’s who actively sought knowledge of NGx through communication with one another and the broader scientific community. They considered NGx an extension of current practice and believed RD’s had the skills to deliver it. Perceived barriers to widening the application of NGx were linked to skepticism among the wider dietetics community. Proliferation of unregulated websites offering tests and diets was considered ‘pseudoscience’ and detrimental to dietetics fully embracing NGx. The lack of a sustainable public health model for the delivery of NGx was also perceived to hinder progress. Results are discussed with reference to ‘diffusion of innovation theory’. Originality/Value - The views of RD’s who practice NGx have not been previously studied. These data highlight requirements for future dietetic training provision and more inclusive service delivery models. Regulation of NGx services and formal recognition by professional bodies is needed to address the research/practice translation gap

Orientifolds of K3 and Calabi-Yau Manifolds with Intersecting D-branes

We investigate orientifolds of type II string theory on K3 and Calabi-Yau 3-folds with intersecting D-branes wrapping special Lagrangian cycles. We determine quite generically the chiral massless spectrum in terms of topological invariants and discuss both orbifold examples and algebraic realizations in detail. Intriguingly, the developed techniques provide an elegant way to figure out the chiral sector of orientifold models without computing any explicit string partition function. As a new example we derive a non-supersymmetric Standard-like Model from an orientifold of type IIA on the quintic Calabi-Yau 3-fold with wrapped D6-branes. In the case of supersymmetric intersecting brane models on Calabi-Yau manifolds we discuss the D-term and F-term potentials, the effective gauge couplings and the Green-Schwarz mechanism. The mirror symmetric formulation of this construction is provided within type IIB theory. We finally include a short discussion about the lift of these models from type IIB on K3 to F-theory and from type IIA on Calabi-Yau 3-folds to M-theory on G_2 manifolds.Comment: 82 pages, harvmac, 5 figures. v2: references added. v3: T^6 orientifold corrected, JHEP versio

Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult Clinical High Risk Cohort

Early intervention for psychotic disorders, a growing international priority, typically targets help-seeking populations with emerging psychotic (“positive”) symptoms. We assessed the nature of and degree to which treatment of individuals at high risk for psychosis preceded or followed the onset of positive symptoms. The North American Prodrome Longitudinal Study–2 collected psychosocial treatment histories for 745 (98%) of 764 high-risk participants (M age = 18.9, 57% male, 57.5% Caucasian, 19.1% Hispanic) recruited from 8 North American communities. Similar to prior findings, 82% of participants reported psychosocial treatment prior to baseline assessment, albeit with significant variability across sites (71%–96%). Participants first received treatment a median of 1.7 years prior to the onset of a recognizable psychosis-risk syndrome. Only one fourth sought initial treatment in the year following syndrome onset. Although mean sample age differed significantly by site, age at initial treatment (M = 14.1, SD = 5.0) did not. High rates of early treatment prior to syndrome onset make sense in light of known developmental precursors to psychotic disorders but are inconsistent with the low rates of treatment retrospectively reported by first-episode psychosis samples. Findings suggest that psychosis risk studies and clinics may need to more actively recruit and engage symptomatic but non-help-seeking individuals and that community clinicians be better trained to recognize both positive and nonspecific indicators of emerging psychosis. Improved treatments for nonspecific symptoms, as well as the characteristic attenuated positive symptoms, are needed

Global agricultural intensification during climate change: A role for genomics

Summary: Agriculture is now facing the 'perfect storm' of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic-assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change. &gt

Depression and clinical high-risk states: Baseline presentation of depressed vs. non-depressed participants in the NAPLS-2 cohort

Depressed mood appears to be highly prevalent in clinical high risk (CHR) samples. However, many prior CHR studies utilize modest size samples and do not report on the specific impact of depression on CHR symptoms. The aim of the current paper is to investigate the prevalence of depressive disorders and the impact of lifetime depression on baseline clinical presentation and longitudinal outcomes in a large cohort of individuals meeting CHR criteria in the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). Depression was assessed both categorically (via DSM-IV-TR diagnoses) and symptomatically (using a clinician-rated scale of depressive symptoms) within a sample of 764 individuals at CHR and 279 controls. Current and lifetime depressive disorders were highly prevalent (60%) in this sample. Depression diagnoses were associated with more pronounced negative and general symptoms; individuals with remitted depression had significantly less severe negative, disorganized, and general symptoms and better social and role functioning relative to those with current depression. Current mood disturbance, as measured by scores on a clinician-rated symptom scale, contributed beyond the impact of positive and negative symptoms to impairments in social functioning. Both symptomatic and diagnostic baseline depression was significantly associated with decreased likelihood of remission from CHR status; however depression did not differentially distinguish persistent CHR status from transition to psychosis at follow-up. These findings suggest that depressed mood may function as a marker of poor prognosis in CHR, yet effective treatment of depression within this population can yield improvements in symptoms and functioning

Appraising empirical applications of Structuration Theory in management and organization studies

There is an increasing interest in the application of Structuration Theory in the fields of management and organization studies. Based upon a thorough literature review, we have come up with a data-set to assess how Structuration Theory has been used in empirical research. We use three key concepts of this theory (duality of structure, knowledgeability, and time-space) as sensitizing concepts for our analysis. We conclude that the greatest potential of Structuration Theory for management and organization studies is to view it as a process theory that offers a distinct building block for explaining intra and interorganizational change, as exemplified through concepts such as routine, script, genre, practice, and discourse

Application of genomicsassisted breeding for generation of climate resilient crops: progress and prospects

CCAFS Climat