Efficacy of a Topical Formulation Containing Emodepside and Praziquantel (Profender®, Bayer) against Nematodes in Captive Tortoises

Gastrointestinal parasites are commonly diagnosed in captive tortoises. In response, fenbendazole has traditionally been used as an anthelmintic, either in single or repeated doses. However, fenbendazole requires oral administration and the process can be very challenging in some individuals. A topical preparation containing emodepside and praziquantel (Profender®, Bayer, Leverkusen, Germany) is promoted as effective against a broad range of nematodes, trematodes, and cestodes. Although this product is currently only licensed for administration to cats, previous studies have shown positive results with tortoises. The aim of this study was to determine the efficacy of Profender against oxyurid and ascarid parasites in captive tortoises. This was achieved by quantifying nematode eggs per gram (EPG) in feces using a modified McMaster technique before (Day 0) and after (Days 14 and 33) topical application of Profender at a dose rate of 21.5 mg emodepside and 85.5 mg praziquantel per kilogram. Twenty-nine tortoises, representing four different species, were enrolled in this study of which 14 (48%; including Testudo hermanni and Testudo graeca) were positive for intestinal nematodes. Following treatment, the oxyurid EPG was slightly increased on Day 14 but declined significantly by Day 33 (59.7% reduction; P = 0.01), indicating a slow onset of effect and moderate efficacy 33 days posttreatment; however, no conclusions regarding efficacy against ascarids can be drawn from this study. Topical application of emodepside and praziquantel was well tolerated in our tortoise population and, therefore, could be considered as a useful alternative anthelmintic treatment protocol for captive tortoises

A Broken Trust: Lessons from the Vaccine–Autism Wars: Researchers long ago rejected the theory that vaccines cause autism, yet many parents don't believe them. Can scientists bridge the gap between evidence and doubt?

Researchers long ago rejected the theory that vaccines cause autism, yet many parents don't believe them. Can scientists bridge the gap between evidence and doubt

Epidermal Stem Cells Are Defined by Global Histone Modifications that Are Altered by Myc-Induced Differentiation

Activation of Myc induces epidermal stem cells to exit their niche and differentiate into sebocytes and interfollicular epidermis, a process that is associated with widespread changes in gene transcription. We have identified chromatin modifications that are characteristic of epidermal stem cells and investigated the effects of Myc activation. Quiescent stem cells in the interfollicular epidermis and the hair follicle bulge had high levels of tri-methylated histone H3 at lysine 9 and H4 at lysine 20. Chromatin in both stem cell populations was hypoacteylated at histone H4 and lacked mono-methylation of histone H4 at lysine 20. Myc-induced exit from the stem cell niche correlated with increased acetylation at histone H4 and transiently increased mono-methylation at lysine 20. The latter was replaced by epigenetic modifications that are largely associated with chromatin silencing: di-methylation at histone H3 lysine 9 and histone H4 lysine 20. These modifications correlated with changes in the specific histone methyltransferases Set8 and Ash-1. The Myc-induced switch from mono- to di-methylated H4K20 required HDAC activity and was blocked by the HDAC inhibitor trichostatin A (TSA). TSA treatment induced a similar epidermal phenotype to activation of Myc, and activation of Myc in the presence of TSA resulted in massive stimulation of terminal differentiation. We conclude that Myc-induced chromatin modifications play a major role in Myc-induced exit from the stem cell compartment

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively) CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel

Cyclic Force Applied to FAs Induces Actin Recruitment Depending on the Dynamic Loading Pattern

Mechanical forces acting on focal adhesions (FAs) are believed to be an important determinant for cytoskeletal reorganization. However, the effect of the temporal pattern of forces on cellular responses has not been elucidated. In the present study, we examined the responses of FAs to locally-applied cyclic forces. Magnetic micro beads coated with fibronectin were attached to the apical surface of endothelial cells and continuous or cyclic forces at frequencies of 0.1-10 Hz with duty cycles of 0-100% were applied to the beads using a newly developed electromagnetic tweezer. A significant increase in actin recruitment around the beads was observed when cyclic forces at 1-2 Hz and 25-50% duty cycles were applied. This tendency disappeared upon modification of myosin activity. These results indicate that the sensitivity to temporal patterns of forces is detemined by the viscoelastic properes of FAs and depends on myosin activity

Continued Neurogenesis in Adult Drosophila as a Mechanism for Recruiting Environmental Cue-Dependent Variants

Background The skills used by winged insects to explore their environment are strongly dependent upon the integration of neurosensory information comprising visual, acoustic and olfactory signals. The neuronal architecture of the wing contains a vast array of different sensors which might convey information to the brain in order to guide the trajectories during flight. In Drosophila, the wing sensory cells are either chemoreceptors or mechanoreceptors and some of these sensors have as yet unknown functions. The axons of these two functionally distinct types of neurons are entangled, generating a single nerve. This simple and accessible coincidental signaling circuitry in Drosophila constitutes an excellent model system to investigate the developmental variability in relation to natural behavioral polymorphisms. Methodology/Principal Findings A fluorescent marker was generated in neurons at all stages of the Drosophila life cycle using a highly efficient and controlled genetic recombination system that can be induced in dividing precursor cells (MARCM system, flybase web site). It allows fluorescent signals in axons only when the neuroblasts and/or neuronal cell precursors like SOP (sensory organ precursors) undergo division during the precedent steps. We first show that a robust neurogenesis continues in the wing after the adults emerge from the pupae followed by an extensive axonal growth. Arguments are presented to suggest that this wing neurogenesis in the newborn adult flies was influenced by genetic determinants such as the frequency dependent for gene and by environmental cues such as population density. Conclusions We demonstrate that the neuronal architecture in the adult Drosophila wing is unfinished when the flies emerge from their pupae. This unexpected developmental step might be crucial for generating non-heritable variants and phenotypic plasticity. This might therefore constitute an advantage in an unstable ecological system and explain much regarding the ability of Drosophila to robustly adapt to their environment

Equity in development and access to health services in the Wild Coast of South Africa: the community view through four linked cross-sectional studies between 1997 and 2007

<p>Abstract</p> <p>Background</p> <p>After election in 1994, the South African government implemented national and regional programmes, such as the Wild Coast Spatial Development Initiative (SDI), to provoke economic growth and to decrease inequities. CIET measured development in the Wild Coast region across four linked cross-sectional surveys (1997-2007). The 2007 survey was an opportunity to look at inequities since the original 1997 baseline, and how such inequities affect access to health care.</p> <p>Methods</p> <p>The 2000, 2004 and 2007 follow-up surveys revisited the communities of the 1997 baseline. Household-level multivariate analysis looked at development indicators and access to health in the context of inequities such as household crowding, access to protected sources of water, house roof construction, main food item purchased, and perception of community empowerment. Individual multivariate models accounted for age, sex, education and income earning opportunities.</p> <p>Results</p> <p>Overall access to protected sources of water increased since the baseline (from 20% in 1997 to 50% in 2007), yet households made of mud and grass, and households who bought basics as their main food item were still less likely to have protected sources of water. The most vulnerable, such as those with less education and less water and food security, were also less likely to have worked for wages leaving them with little chance of improving their standard of living (less education OR 0.59, 95%CI 0.37-0.94; less water security OR 0.67, 95%CI 0.48-0.93; less food security OR 0.43, 95%CI 0.29-0.64). People with less income were more likely to visit government services (among men OR 0.28, 95%CI 0.13-0.59; among women OR 0.33, 95%CI 0.20-0.54), reporting decision factors of cost and distance; users of private clinics sought out better service and medication. Lower food security and poorer house construction was also associated with women visiting government rather than private health services. Women with some formal education were nearly eight times more likely than women with no education to access health services for prevention rather than curative reasons (OR 7.65, 95%CI 4.10-14.25).</p> <p>Conclusion</p> <p>While there have been some improvements, the Wild Coast region still falls well below provincial and national standards in key areas such as access to clean water and employment despite years of government-led investment. Inequities remain prominent, particularly around access to health services.</p

Controlling behavior, power relations within intimate relationships and intimate partner physical and sexual violence against women in Nigeria

<p>Abstract</p> <p>Background</p> <p>Controlling behavior is more common and can be equally or more threatening than physical or sexual violence. This study sought to determine the role of husband/partner controlling behavior and power relations within intimate relationships in the lifetime risk of physical and sexual violence in Nigeria.</p> <p>Methods</p> <p>This study used secondary data from a cross-sectional nationally-representative survey collected by face-to-face interviews from women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey. Utilizing a stratified two-stage cluster sample design, data was collected frrm 19 216 eligible with the DHS domestic violence module, which is based on the Conflict Tactics Scale (CTS). Multivariate logistic regression analysis was used to determine the role of husband/partner controlling behavior in the risk of ever experiencing physical and sexual violence among 2877 women aged 15 - 49 years who were currently or formerly married or cohabiting with a male partner.</p> <p>Results</p> <p>Women who reported controlling behavior by husband/partner had a higher likelihood of experiencing physical violence (RR = 3.04; 95% CI: 2.50 - 3.69), and women resident in rural areas and working in low status occupations had increased likelihood of experiencing physical IPV. Controlling behavior by husband/partner was associated with higher likelihood of experiencing physical violence (RR = 4.01; 95% CI: 2.54 - 6.34). In addition, women who justified wife beating and earned more than their husband/partner were at higher likelihood of experiencing physical and sexual violence. In contrast, women who had decision-making autonomy had lower likelihood of experiencing physical and sexual violence.</p> <p>Conclusion</p> <p>Controlling behavior by husband/partner significantly increases the likelihood of physical and sexual IPV, thus acting as a precursor to violence. Findings emphasize the need to adopt a proactive integrated approach to controlling behavior and intimate partner violence within the society.</p

Insect Repellents: Modulators of Mosquito Odorant Receptor Activity

Background: DEET, 2-undecanone (2-U), IR3535 and Picaridin are widely used as insect repellents to prevent interactions between humans and many arthropods including mosquitoes. Their molecular action has only recently been studied, yielding seemingly contradictory theories including odorant-dependent inhibitory and odorant-independent excitatory activities on insect olfactory sensory neurons (OSNs) and odorant receptor proteins (ORs). Methodology/Principal Findings: Here we characterize the action of these repellents on two Aedes aegypti ORs, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes; these ORs are respectively activated by the odors indole (AaOR2) and (R)-(2)-1-octen3-ol (AaOR8), odorants used to locate oviposition sites and host animals. In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs. Conclusions/Significance: These data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models