Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2

PURPOSE: To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO). METHODS: Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified. RESULTS: By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane. CONCLUSIONS: Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging. TRANSLATIONAL RELEVANCE: The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

When Flexibility Is Stable: Implicit Long-Term Shaping of Olfactory Preferences

Preferences are traditionally assumed to be stable. However, empirical evidence such as preference modulation following choices calls this assumption into question. The evolution of such postchoice preference over long time spans, even when choices have been explicitly forgotten, has so far not been studied. In two experiments, we investigated this question by using a variant of the free choice paradigm: In a first session, participants evaluated the pleasantness of a number of odors. We then formed pairs of similarly rated odors, and asked participants to choose their favorite, for each pair. Participants were then presented with all odors again, and asked for another pleasantness rating. In a second session 1 week later, a third pleasantness rating was obtained, and participants were again asked to choose between the same options. Results suggested postchoice preference modulation immediately and 1 week after choice for both chosen and rejected options, even when choices were not explicitly remembered. A third experiment, using another paradigm, confirmed that choice can have a modulatory impact on preferences, and that this modulation can be long-lasting. Taken together, these findings suggest that although preferences appear to be flexible because they are modulated by choices, this modulation also appears to be stable over time and even without explicit recollection of the choice. These results bring a new argument to the idea that postchoice preference modulation could rely on implicit mechanisms, and are consistent with the recent proposal that cognitive dissonance reduction could to some extent be implicit

Ethnicity coding in a regional cancer registry and in Hospital Episode Statistics

BACKGROUND: The collection of ethnicity information as part of cancer datasets is important for planning services and ensuring equal access, and for epidemiological studies. However, ethnicity has generally not been well recorded in cancer registries in the UK. The aim of this study was to determine the completeness of ethnicity coding in the Thames Cancer Registry (TCR) database and within the Hospital Episode Statistics (HES) data as held by the London Health Observatory, and to investigate factors associated with ethnicity being recorded. METHODS: Records for 111821 hospital admissions of London residents with a malignant cancer as a primary diagnosis between April 2002 and March 2003 and records for 25581 London residents diagnosed with cancer in 2002 were examined. Data on sex, age, cancer network of residence, deprivation, proportion of non-whites in the local authority population, and site of cancer were available. The proportion of patients in each group with a valid ethnicity code was calculated. In the TCR data proportions were also calculated adjusted for all other variables. RESULTS: Ethnicity was recorded for 90661 (81.1%) of the hospital admissions in the HES data and 5796 (22.7%) patients on the TCR database. Patients resident in areas with a higher proportion of non-white residents and the most deprived populations were more likely to have an ethnic code on the TCR database, though this pattern was not seen in the HES data. Adjustment did not materially affect the association between deprivation and ethnicity being recorded in the TCR data. CONCLUSION: There was a large difference in completeness of ethnicity between the data sources. In order to improve the level of recording in TCR data there needs to be better recording of ethnicity in sources TCR data collection staff have access to, or use of information from other sources e.g. electronic data feeds from hospitals or pathology laboratories, or HES data itself supplied directly to TCR. Efforts to collect ethnicity data should be encouraged in all healthcare settings. Future research should explore where the difficulties collecting ethnicity information lie, whether with patients, healthcare professionals or the recording procedure, and how such problems can be overcome

Awareness of vitamin D deficiency among at-risk patients

<p>Abstract</p> <p>Background</p> <p>Vitamin D deficiency is a significant problem for a growing proportion of the UK population. Individuals with dark or covered skin are at particularly high risk due to ethno-cultural, environmental and genetic factors. We assessed the level of awareness of vitamin D deficiency among at-risk patients in order to identify groups most in need of education.</p> <p>Findings</p> <p>A cross-sectional survey using a piloted questionnaire was conducted among consecutive at-risk patients without a diagnosis of Vitamin D deficiency arriving at a large inner city general practice in the North West of England over a five day period. The survey was completed by 221 patients. The mean age was 35 years. 28% of them (n = 61) had never heard about vitamin D. Older patients (p = 0.003) were less likely to have heard about vitamin D. 54% of participants were unaware of the commonest symptoms of vitamin D deficiency. 34% did not expose their skin other than their face in the last one year, and 11% did not include vitamin D rich foods in their diet.</p> <p>Conclusion</p> <p>The majority of at-risk patients are aware of vitamin D; nevertheless, there is a significant lack of knowledge among older people, who have higher morbidity. A programme of targeted education of the at-risk population is recommended.</p

The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.&lt;p&gt;&lt;/p&gt; Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.&lt;p&gt;&lt;/p&gt; Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.&lt;p&gt;&lt;/p&gt; Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.&lt;p&gt;&lt;/p&gt