The ChromaTest, a digital color contrast sensitivity analyzer, for diabetic maculopathy: a pilot study

BACKGROUND: To assess the ability of the Chromatest in investigating diabetic maculopathy. METHOD: Patients with Type 2 diabetes and no concurrent ocular pathology or previous laser photocoagulation were recruited. Visual acuities were assessed followed by colour contrast sensitivity testing of each eye using Chromatest. Dilated fundoscopy with slit lamp biomicroscopy with 78 D lens was then performed to confirm the stage of diabetic retinopathy according to the Early Treatment Diabetic Retinopathy Study. RESULTS: 150 eyes in 150 patients were recruited into this study. 35 eyes with no previous laser photocoagulation were shown to have clinically significant macular oedema (CSMO) and 115 eyes with untreated non-proliferative diabetic retinopathy (NPDR) on fundus biomicroscopy. Statistical significant difference was found between CSMO and NPDR eyes for protan colour contrast threshold (p = 0.01). Statistical significance was found between CSMO and NPDR eyes for tritan colour contrast threshold (p = 0.0002). Sensitivity and specificity for screening of CSMO using pass-fail criterion for age matched TCCT results achieved 71% (95% confidence interval: 53-85%) and 70% (95% confidence interval: 60-78%), respectively. However, threshold levels were derived using the same data set for both training and testing the effectiveness since this was the first study of NPDR using the Chromatest CONCLUSION: The ChromaTest is a simple, cheap, easy to use, and quick test for colour contrast sensitivity. This study did not achieve results to justify use of the Chromatest for screening, but it reinforced the changes seen in tritan colour vision in diabetic retinopathy

Social Networking Technology, Social Network Composition, and Reductions in Substance Use Among Homeless Adolescents

Peer-based prevention programs for homeless youth are complicated by the potential for reinforcing high-risk behaviors among participants. The goal of this study is to understand how homeless youth could be linked to positive peers in prevention programming by understanding where in social and physical space positive peers for homeless youth are located, how these ties are associated with substance use, and the role of social networking technologies (e.g., internet and cell phones) in this process. Personal social network data were collected from 136 homeless adolescents in Los Angeles, CA. Respondents reported on composition of their social networks with respect to: home-based peers and parents (accessed via social networking technology; e.g., the internet, cell phone, texting), homeless peers and agency staff (accessed face-to-face) and whether or not network members were substance-using or non-substance-using. Associations between respondent’s lifetime cocaine, heroin, and methamphetamine use and recent (previous 30 days) alcohol and marijuana use were assessed by the number of non-substance-using versus substance-using ties in multivariate linear regression models. 43% of adolescents reported a non-substance-using home-based tie. More of these ties were associated with less recent alcohol use. 62% of adolescents reported a substance-using homeless tie. More of these ties were associated with more recent marijuana use as well as more lifetime heroin and methamphetamine use. For homeless youth, who are physically disconnected from positive peers, social networking technologies can be used to facilitate the sorts of positive social ties that effective peer-based prevention programs require

Selective and Irreversible Inhibitors of Mosquito Acetylcholinesterases for Controlling Malaria and Other Mosquito-Borne Diseases

New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 µM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast (∼30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species

Mono- versus polydrug abuse patterns among publicly funded clients

To examine patterns of mono- versus polydrug abuse, data were obtained from intake records of 69,891 admissions to publicly funded treatment programs in Tennessee between 1998 and 2004. While descriptive statistics were employed to report frequency and patterns of mono- and polydrug abuse by demographic variables and by study years, bivariate logistic regression was applied to assess the probability of being a mono- or polydrug abuser for a number of demographic variables. The researchers found that during the study period 51.3% of admissions reported monodrug abuse and 48.7% reported polydrug abuse. Alcohol, cocaine, and marijuana were the most commonly abused substances, both alone and in combination. Odds ratio favored polydrug abuse for all but one drug category–other drugs. Gender did not affect drug abuse patterns; however, admissions for African Americans and those living in urban areas exhibited higher probabilities of polydrug abuse. Age group also appeared to affect drug abuse patterns, with higher odds of monodrug abuse among minors and adults over 45 years old. The discernable prevalence of polydrug abuse suggests a need for developing effective prevention strategies and treatment plans specific to polydrug abuse

Modulation of the immune response by nematode secreted acetylcholinesterase revealed by heterologous expression in Trypanosoma musculi

Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host

Mouse Acetylcholinesterase Enhances Neurite Outgrowth of Rat R28 Cells Through Interaction With Laminin-1

The enzyme acetylcholinesterase (AChE) terminates synaptic transmission at cholinergic synapses by hydrolyzing the neurotransmitter acetylcholine, but can also exert ‘non-classical’, morpho-regulatory effects on developing neurons such as stimulation of neurite outgrowth. Here, we investigated the role of AChE binding to laminin-1 on the regulation of neurite outgrowth by using cell culture, immunocytochemistry, and molecular biological approaches. To explore the role of AChE, we examined fiber growth of cells overexpressing different forms of AChE, and/or during their growth on laminin-1. A significant increase of neuritic growth as compared with controls was observed for neurons over-expressing AChE. Accordingly, addition of globular AChE to the medium increased total length of neurites. Co-transfection with PRIMA, a membrane anchor of AChE, led to an increase in fiber length similar to AChE overexpressing cells. Transfection with an AChE mutant that leads to the retention of AChE within cells had no stimulatory effect on neurite length. Noticeably, the longest neurites were produced by neurons overexpressing AChE and growing on laminin-1, suggesting that the AChE/laminin interaction is involved in regulating neurite outgrowth. Our findings demonstrate that binding of AChE to laminin-1 alters AChE activity and leads to increased neurite growth in culture. A possible mechanism of the AChE effect on neurite outgrowth is proposed due to the interaction of AChE with laminin-1

Evaluation of the impact of interdisciplinarity in cancer care

<p>Abstract</p> <p>Background</p> <p>Teamwork is a key component of the health care renewal strategy emphasized in Quebec, elsewhere in Canada and in other countries to enhance the quality of oncology services. While this innovation would appear beneficial in theory, empirical evidences of its impact are limited. Current efforts in Quebec to encourage the development of local interdisciplinary teams in all hospitals offer a unique opportunity to assess the anticipated benefits. These teams working in hospital outpatient clinics are responsible for treatment, follow-up and patient support. The study objective is to assess the impact of interdisciplinarity on cancer patients and health professionals.</p> <p>Methods/Design</p> <p>This is a quasi-experimental study with three comparison groups distinguished by intensity of interdisciplinarity: strong, moderate and weak. The study will use a random sample of 12 local teams in Quebec, stratified by intensity of interdisciplinarity. The instrument to measure the intensity of the interdisciplinarity, developed in collaboration with experts, encompasses five dimensions referring to aspects of team structure and process. Self-administered questionnaires will be used to measure the impact of interdisciplinarity on patients (health care utilization, continuity of care and cancer services responsiveness) and on professionals (professional well-being, assessment of teamwork and perception of teamwork climate). Approximately 100 health professionals working on the selected teams and 2000 patients will be recruited. Statistical analyses will include descriptive statistics and comparative analysis of the impact observed according to the strata of interdisciplinarity. Fixed and random multivariate statistical models (multilevel analyses) will also be used.</p> <p>Discussion</p> <p>This study will pinpoint to what extent interdisciplinarity is linked to quality of care and meets the complex and varied needs of cancer patients. It will ascertain to what extent interdisciplinary teamwork facilitated the work of professionals. Such findings are important given the growing prevalence of cancer and the importance of attracting and retaining health professionals to work with cancer patients.</p

A New Direction to Athletic Performance: Understanding the Acute and Longitudinal Responses to Backward Running

Backward running (BR) is a form of locomotion that occurs in short bursts during many overground field and court sports. It has also traditionally been used in clinical settings as a method to rehabilitate lower body injuries. Comparisons between BR and forward running (FR) have led to the discovery that both may be generated by the same neural circuitry. Comparisons of the acute responses to FR reveal that BR is characterised by a smaller ratio of braking to propulsive forces, increased step frequency, decreased step length, increased muscle activity and reliance on isometric and concentric muscle actions. These biomechanical differences have been critical in informing recent scientific explorations which have discovered that BR can be used as a method for reducing injury and improving a variety of physical attributes deemed advantageous to sports performance. This includes improved lower body strength and power, decreased injury prevalence and improvements in change of direction performance following BR training. The current findings from research help improve our understanding of BR biomechanics and provide evidence which supports BR as a useful method to improve athlete performance. However, further acute and longitudinal research is needed to better understand the utility of BR in athletic performance programs

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms