FMRFamide-related peptides (FaRPs) in helminth parasites

Neuropeptides are ubiquitous intercellular signalling molecules in all Metazoa with nervous systems. Research over the past 10 years has confirmed through immunocytochemistry that neuropeptides are widespread and abundant in the nervous systems of helminth parasites. Biochemical isolation and characterisation studies have indentified the primary structures of numerous structurally-related peptides in helminths, the best studied being the FMRFamide-related peptides (FaRPs). While to date only four FaRPs have been identified from platyhelminths, some 60 FaRPs or FaRP-like peptides have been isolated or predicted for nematodes. Preliminary physiological studies have shown that FaRPs are strongly myoactive, but with quire different actions in the two groups of helminth parasite. The absence of FaRPs from vertebrates suggests compounds with a high affinity for FaRP receptors are likely to have selective effects against helminths and, if protected from degradation, could have therapeutic potential.

Platyhelminth FMRFamide-related peptides

Platyhelminths are the most primitive metazoan phylum to possess a true central nervous system, comprising a brain and longitudinal nerve cords connected by commissures. Additional to the presence of classical neurotransmitters, the nervous systems of all major groups of flatworms examined have widespread and abundant peptidergic components, Decades of research on the major invertebrate phyla, Mollusca and Arthropoda, have revealed the primary structures and putative functions of several families of structurally related peptides, the best studied being the FMRFamide-related peptides (FaRPs). Recently, the first platyhelminth FaRP was isolated from the tapeworm, Moniezia expansa, and was found to be a hexapeptide amide, GNFFRFamide. Two additional PaRPs were isolated from species of turbellarians; these were pentapeptides, RYIRFamide (Artioposthia triangulata) and GYIRFamide (Dugesia tigrina). The primary structure of a monogenean or digenean FaRP has yet to be deduced. Preliminary physiological studies have shown that both of the turbellarian FaRPs elicit dose-dependent contractions of isolated digenean and turbellarian somatic muscle fibres. Unlike the high structural diversity of FaRPs found in molluscs, arthropods and nematodes, the complement of FaRPs in individual species of platyhelminths appears to be restricted to 1 or 2 related molecules. Much remains to be learnt about platyhelminth PaRPs, particularly from peptide isolation, molecular cloning of precursor proteins, receptor localization, and physiological studies. Copyright (C) 1996 Australian Society for Parasitology.

GENOTYPE-PHENOTYPE ASSOCIATIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE:To examine associations between recognized genetic susceptibility loci and angiographic subphenotypes of the neovascular variant of age-related macular degeneration (nvAMD).METHODS:Participants (247 nvAMD, 52 early age-related macular degeneration [AMD], and 103 controls) were genotyped (complement factor H and ARMS2/HTRA1). nvAMD participants were assigned to one of two subcategories: mainly classic or mainly occult (based on the proportions of classic and occult choroidal neovascularization). nvAMD and early AMD were reassigned to two groups based on the extent and severity of drusen (retinal pigment epithelium dysfunction or not). Univariate and multivariate analysis were used to examine for associations between participant characteristics and genetic loci after adjusting for age, smoking status, and history of cardiovascular disease.RESULTS:Univariate analysis confirmed the known significant associations between AMD stage and age, hypertension, and a history of cardiovascular disease. Those with retinal pigment epithelium dysfunction (F = 5.46; P = 0.02) or a positive smoking history (F = 3.89; P = 0.05) were more likely to have been classified as having mainly an occult rather than a mainly classic lesion. Multivariate analysis showed that significant associations were noted with the number of ARMS2/HTRA1 risk alleles (P

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

Purpose
To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).

Design
Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).

Participants
People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart.

Methods
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.

Main Outcome Measures
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.

Results
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).

Conclusions
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.

Financial Disclosure(s)
Proprietary or commercial disclosures may be found after the references.

Exploring and comparing the experience and coping behaviour of men and women with colorectal cancer at diagnosis and during surgery

Aim. This paper is a report of a study exploring and comparing the experience of men and women with colorectal cancer at diagnosis and during surgery.

Background. Men have higher incidence and mortality rates for nearly all cancers and frequently use health behaviours that reflect their masculinity. There has been minimal investigation into the influence of gender on the experience of a ‘shared’ cancer.

Methods. From November 2006 to November 2008, a qualitative study was conducted involving 38 individuals (24 men, 14 women) with colorectal cancer. Data were generated using semi-structured interviews at four time points over an 18-month period. This paper reports the participants’ experience at diagnosis and during surgery (time point 1) with the purpose of examining the impact of gender on this experience.

Findings. In general, men appeared more accepting of their diagnosis. The majority of females seemed more emotional and more affected by the physical side effects. However, there was variation in both gender groups, with some men and women portraying both ‘masculine’ and ‘feminine’ traits. There was also individual variation in relation to context.

Conclusions. It appears that many men may have been experiencing side effects and/or psychological distress that they were reluctant to discuss, particularly as some men portrayed typical ‘masculine’ traits in public, but felt able to open up in private. Nurses should not make assumptions based on the traditional view of masculinity, and should determine how each man wants to deal with their diagnosis and not presume that all men need to ‘open up’ about their illness.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 EURODIAB centres during 1989-2008

Objectives: To investigate seasonal variation in month of diagnosis in children with type 1 diabetes registered in EURODIAB centres during 1989-2008.
Methods: 23 population-based registers recorded date of diagnosis in new cases of clinically diagnosed type 1 diabetes in children aged under 15 years. Completeness of ascertainment was assessed through capture-recapture methodology and was high in most centres. A general test for seasonal variation (11df) and Edward's test for sinusoidal (sine wave) variation (2df) were employed. Time series methods were also used to investigate if meteorological data were predictive of monthly counts after taking account of seasonality and long term trends.
Results: Significant seasonal variation was apparent in all but two small centres, with an excess of cases apparent in the winter quarter. Significant sinusoidal pattern was also evident in all but two small centres with peaks in December (14 centres), January (5 centres) or February (2 centres). Relative amplitude varied from ±11% to ±39% (median ±18%). There was no relationship across the centres between relative amplitude and incidence level. However there was evidence of significant deviation from the sinusoidal pattern in the majority of centres. Pooling results over centres, there was significant seasonal variation in each age-group at diagnosis, but with significantly less variation in those aged under 5 years. Boys showed marginally greater seasonal variation than girls. There were no differences in seasonal pattern between four sub-periods of the 20 year period. In most centres monthly counts of cases were not associated with deviations from normal monthly average temperature or sunshine hours; short term meteorological variations do not explain numbers of cases diagnosed.
Conclusions: Seasonality with a winter excess is apparent in all age-groups and both sexes, but girls and the under 5s show less marked variation. The seasonal pattern changed little in the 20 year period.

ARMS2 Increases the Risk of Early and Late Age-Related Macular Degeneration in the European Eye Study

OBJECTIVE:
To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.
DESIGN:
Population-based, cross-sectional European Eye Study in 7 countries in Europe.
PARTICIPANTS:
Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
METHODS:
Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.
MAIN OUTCOME MEASURES:
Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
RESULTS:
Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).
CONCLUSIONS:
A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.

Catheter-related bloodstream infection in adult haematology patients:Catheter removal practice and outcome

The aim of the present study was to describe the practice of central venous catheter (CVC) removal and outcomes of catheter-related bloodstream infection (CR-BSI) in adult haematology patients. Patients were identified retrospectively according to diagnosis coding of inpatient episodes and evaluated when, on examination of medical records, there had been evidence of sepsis with strong clinical suspicion that the source was the CVC. Demographic and bacteriological data, as well as therapeutic measures and clinical outcomes, were recorded. One hundred and three patient episodes were evaluated. The most frequent type of CVC was the Hickman catheter and the most frequently isolated pathogen was coagulase-negative staphylococci. Twenty-five percent of episodes were managed with catheter removal. Treatment failure, defined as recurrence of infection within 90 days or mortality attributed to sepsis within 30 days, occurred significantly more frequently in the group managed without catheter removal (52.5% versus 4%, P

Effect of preventive primary care outreach on health related quality of life among older adults at risk of functional decline: Randomised controlled trial

Objective: To evaluate the impact of a provider initiated primary care outreach intervention compared with usual care among older adults at risk of functional decline. Design: Randomised controlled trial. Setting: Patients enrolled with 35 family physicians in five primary care networks in Hamilton, Ontario, Canada. Participants Patients: were eligible if they were 75 years of age or older and were not receiving home care services. Of 3166 potentially eligible patients, 2662 (84%) completed the validated postal questionnaire used to determine risk of functional decline. Of 1724 patients who met the risk criteria, 769 (45%) agreed to participate and 719 were randomised. Intervention: The 12 month intervention, provided by experienced home care nurses in 2004-6, consisted of a comprehensive initial assessment using the resident assessment instrument for home care; collaborative care planning with patients, their families, and family physicians; health promotion; and referral to community health and social support services. Main outcome measures: Quality adjusted life years (QALYs), use and costs of health and social services, functional status, self rated health, and mortality. Results: The mean difference in QALYs between intervention and control patients during the study period was not statistically significant (0.017, 95% confidence interval -0.022 to 0.056; P=0.388). The mean difference in overall cost of prescription drugs and services between the intervention and control groups was not statistically significant, (-$C165 (£107; €118; $162), 95% confidence interval -$C16 545 to $C16 214; P=0.984). Changes over 12 months in functional status and self rated health were not significantly different between the intervention and control groups. Ten patients died in each group. Conclusions: The results of this study do not support adoption of this preventive primary care intervention for this target population of high risk older adults. Trial registration: Clinical trials NCT00134836.

Secondary Outcomes in a Clinical Trial of Carotenoids with Coantioxidants versus Placebo in Early Age-Related Macular Degeneration

Purpose: To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.

Design: Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).

Participants: Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2).

Intervention: An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months.

Main Outcome Measures: Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months).

Results: The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed.

Conclusions: Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Age-related reference intervals for lymphocyte subsets in whole blood of healthy individuals

Enumeration of various lymphocyte subsets is used widely in the diagnosis and monitoring of various disease states. With the development of flow cytometric technology and whole blood analysis, methodologies have become more sensitive. It is therefore important to establish reference intervals in normal, healthy individuals using these techniques to give a better indication of the border between health and disease. Since some lymphocyte subpopulations are known to change with age, we have enumerated common subsets in healthy individuals from all decades of adult life, including nonagenarian subjects. We report reference intervals for these subsets in each age group, which will be of use in diagnosis and disease monitoring, particularly in elderly subjects, the most rapidly expanding group within the population today.

Identifying Economically Vulnerable Groups as the Economic Crisis Emerged

A frequent refrain during recent debates on welfare cuts and tax increases has related to the need to "protect the vulnerable". However, it is far from clear that a consensus exists on which individuals or groups are to be included under this heading with a consequent lack of clarity for the policy implications of pursuing this goal. In this paper, operating with a conception of social exclusion that incorporates notions of dynamics and multidimensionality, we make use of EU-SILC 2008 data for Ireland to clarify the distinction between income poverty and economic vulnerability. We then proceed to consider the relationship between these outcomes and multiple deprivation, financial pressures and perceptions of recent and future economic prospects. Our analysis is then extended to compare patterns of risk for poverty and vulnerability in relation to key socio-economic groups. Finally, we will consider the relationship between poverty and vulnerability and the distribution of welfare dependence. Our analysis suggests that the vulnerable but non-poor group may need to be a key focus of policy attention in the future.

Accessibility and availability of smoking-related associations in smokers

A free association test was used in the present study to examine the availability and accessibility of positive vs negative smoking-related information in the long-term memories of smokers. Participants were asked to generate smoking-related associations across a 4-minute interval. Although smokers generated more positive smoking-associations than non-smokers, both groups produced a greater number of negative than positive associations per se. Of particular interest was the finding that whilst the ratio of positive/negative associations generated was constant across time in non-smokers, this ratio varied in smokers. Specifically, smokers generated proportionately more of their available positive associations and proportionately less of their negative associations in the early time interval. It is suggested that these results not only indicate a greater availability of positive smoking-associations in smokers compared to non-smokers, but also a greater accessibility too. It is proposed that positive smoking associations are more automatically activated than negative associations in smokers, even though they have generally more negative associations available.

Visual outcomes in the subfoveal radiotherapy study:A randomized controlled trial of teletherapy for age-related macular degeneration

Objective: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. Design: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. Setting: Three United Kingdom-based hospital units. Participants: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. Methods: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. Main Outcome Measures: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. Results: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P=.08) or 6 or more (severe) (P=.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P=.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P=.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. Conclusion: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

Adsorption of metal cations by hydrous aluminium(III) or iron(III) hydroxide precipitates: enhancement by EDTA and related chelate molecules

Stoichiometrically equivalent concentrations of ethylenediaminetetraacetate, EDTA, and of related chelating anions increase the adsorption of ca. millimolar concentrations heavy metal aqua-ions on amorphous precipitates of aluminium(III) or iron(III) hydroxide and, although higher concentrations decrease the adsorption, poly-EDTA, a polyelectrolyte containing EDTA functional groups, shows no such decrease.