Noninvasive Assessment of Photoreceptor Structure and Function in the Human Retina

The human photoreceptor mosaic underlies the first steps of vision; thus, even subtle defects in the mosaic can result in severe vision loss. The retina can be examined directly using clinical tools; however these devices lack the resolution necessary to visualize the photoreceptor mosaic. The primary limiting factor of these devices is the optical aberrations of the human eye. These aberrations are surmountable with the incorporation of adaptive optics (AO) to ophthalmoscopes, enabling imaging of the photoreceptor mosaic with cellular resolution. Despite the potential of AO imaging, much work remains before this technology can be translated to the clinic. Metrics used in the analysis of AO images are not standardized and are rarely subjected to validation, limiting the ability to reliably track structural changes in the photoreceptor mosaic geometry. Preceding the extraction of measurements, photoreceptors must be identified within the retinal image itself. This introduces error from both incorrectly identified cells and image distortion. We developed a novel method to extract measures of cell spacing from AO images that does not require identification of individual cells. In addition, we examined the sensitivity of various metrics in detecting changes in the mosaic and assessed the absolute accuracy of measurements made in the presence of image distortion. We also developed novel metrics for describing the mosaic, which may offer advantages over more traditional metrics of density and spacing. These studies provide a valuable basis for monitoring the photoreceptor mosaic longitudinally. As part of this work, we developed software (Mosaic Analytics) that can be used to standardize analytical efforts across different research groups. In addition, one of the more salient features of the appearance of individual cone photoreceptors is that they vary considerably in their reflectance. It has been proposed that this reflectance signal could be used as a surrogate measure of cone health. As a first step to understanding the cellular origin of these changes, we examined the reflectance properties of the rod photoreceptor mosaic. The observed variation in rod reflectivity over time suggests a common governing physiological process between rods and cones

What makes you not a Sikh? : a preliminary mapping of values

This study sets out to establish which Sikh values contrasted with or were shared by non-Sikh adolescents. A survey of attitude toward a variety of Sikh values was fielded in a sample of 364 non-Sikh schoolchildren aged between 13 and 15 in London. Values where attitudes were least positive concerned Sikh duties/code of conduct, festivals, rituals, prayer Gurdwara attendance, listening to scripture recitation, the amrit initiation. Sikh values empathized with by non-Sikhs concerned family pride, charity, easy access to ordination and Gurdwaras, maintaining the five Ks, seeing God in all things, abstaining from meat and alcohol and belief in the stories of Guru Nanak. Further significant differences of attitude toward Sikhism were found in comparisons by sex, age and religious affiliation. Findings are applied to teaching Sikhism to pupils of no faith adherence. The study recommends the extension of values mapping to specifically Sikh populations

Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol hydro­bromide]

X-ray crystallographic analysis of the title hydro­bromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxy­lated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae) leaves. In the crystal structure, mol­ecules are linked by inter­molecular O—H⋯Br and N—H⋯Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intra­molecular O—H⋯O inter­actions occur

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight and obese men

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese males [46.4±1.4 years, BMI 32.3±5.4 kg/m2] participated in the acute feeding study, which consisted of 2 randomised crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion) 4h before the coingestion of milk protein, intrinsically labelled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese males [44.0±1.7 years, BMI 30.1±1.1 kg/m2] participated in the chronic study, which consisted of a baseline 1-week isocaloric diet followed by a 2-week high fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was 2-fold higher (P<0.05) in the lipid trial compared to control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, PDC activity and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle DAG C16:0 (P=0.06) and ceramide C16:0 (P<0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

Process theory and research: Exploring the dialectic tension

We contest that although the notion of process is increasingly being applied to the study of organizations, these attempts are hampered by significant methodological shortcomings. We claim that the value of process theory is under-utilized because most attempts to apply process theory end up reverting to conventional non-process methods. We suggest that the cause of this reversion is primarily the challenge of making sense, of fixing the world, propelling us from process into the world of substance. To break free of these limitations we propose an approach that takes the researchers? audience alongside the subject processes rather than attempting to clinically intersect them. We illuminate this paper with our own story vignettes concerning the fortunes of an idea that passes by the name of value based management (VBM). 1 These vignettes are meant to both exemplify and disrupt the theoretical narrative

Contribution of scaling up nutrition Academic Platforms to nutrition capacity strengthening in Africa: local efforts, continental prospects and challenges

Addressing contemporary nutrition problems often require application of knowledge from multiple disciplines. The scaling up nutrition (SUN) movement harnesses multiple sectors for effective global and in-country planning and implementation. Although the role of knowl- edge networks (academia and research institutions) is recognised, the how of engaging knowl- edge networks in the current SUN architecture is only now becoming apparent. For relevant sectors to play their roles effectively, observed capacity gaps, particularly in developing coun- try settings, need to be addressed. The present paper presents the work being undertaken by the Ghana SUN Academic Platform, a local knowledge network, towards strengthening nutrition capacity in Ghana. The Platform presently provides technical support, evidence and capacity towards scaling up effective nutrition interventions in Ghana and beyond. The data presented draws heavily on the observations and collective experiences of the authors in practice, com- plemented by a review of relevant literature. The ultimate goal of the AP is to build capacity of professionals from nutrition and cognate sectors (including planning, agriculture, health, economics, research and academia). This is an essential ingredient for effective and durable SUN efforts. The paper recognises that both disciplinary and interdisciplinary capacity is required for effective SUN efforts in Africa, and offers an approach that utilises cross-sector/inter-professional, peer-learning and experiential learning initiatives

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy : Insights From Wave Intensity Analysis and Magnetic Resonance

Background: Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives: Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods: Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results: Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions: Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment