The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

“Hang in there mama!”: The role of online parenting forums in maternal mental health

The perinatal period can be challenging and yet reluctance to disclose wellbeing concerns to health professionals is well documented. The current study sought to explore how women use online parenting forums to seek advice and support for maternal mental health concerns. Forum threads (n = 153) from a popular UK parenting website were analysed to explore postpartum mothers’ discussions about their maternal mental health. Through reflexive thematic analysis, four themes were generated: (1) Navigating the motherhood role: unprepared and overwhelmed; (2) ‘I’m struggling, but looking on here I know I’m no way alone!’; (3) Challenging feelings of failure: ‘it doesn’t make you a bad mother’; and (4) Forums facilitate help seeking. There were two main findings; first, forums may act as a potential solution to providing a supportive, reassuring community and safe space for disclosure around maternal mental health concerns. Furthermore, forums are beneficial in providing women with an honest, realistic view and expectation of motherhood, thus supporting their transition to parenthood. Consequently, forums could be utilised to inform training for healthcare professionals to understand disclosure barriers

Setting things straight: a comparison of measures of saccade trajectory deviation

In eye movements, saccade trajectory deviation has often been used as a physiological operationalization of visual attention, distraction, or the visual system’s prioritization of different sources of information. However, there are many ways to measure saccade trajectories and to quantify their deviation. This may lead to noncomparable results and poses the problem of choosing a method that will maximize statistical power. Using data from existing studies and from our own experiments, we used principal components analysis to carry out a systematic quantification of the relationships among eight different measures of saccade trajectory deviation and their power to detect the effects of experimental manipulations, as measured by standardized effect size. We concluded that (1) the saccade deviation measure is a good default measure of saccade trajectory deviation, because it is somewhat correlated with all other measures and shows relatively high effect sizes for two well-known experimental effects; (2) more generally, measures made relative to the position of the saccade target are more powerful; and (3) measures of deviation based on the early part of the saccade are made more stable when they are based on data from an eyetracker with a high sampling rate. Our recommendations may be of use to future eye movement researchers seeking to optimize the designs of their studies

"There are hundreds of thousands online waiting to hold your hand through difficult times”: experiences of using online parenting forums to support postpartum mental health and wellbeing.

Background and aims: Internet use in new mothers is common, with increasing numbers of women seeking support online in lieu of consulting health professionals. The current study sought to explore women’s experiences of using online parenting forums to seek advice and support for their maternal mental health. Although benefits of virtual support have previously been highlighted, little research has examined any potential harmful consequences of utilising online forum support for mental health concerns. Methods: New mothers (n=70) completed an online survey as a qualitative account of their motivations for, and experiences of, using online forums. Additionally, mothers were questioned about their experiences of healthcare professional support. Findings: Through reflexive thematic analysis, four themes were generated: (1) The value of shared experiences and empathy; (2) Forum dynamics – a double edged sword; (3) Contextual challenges and opportunities; and (4) Inconsistency of HCP support – the need for an instant solution. Findings emphasised the importance, and effectiveness, of this kind of virtual peer support that forums provide. For many, the responses indicated that forums have a great potential to foster an atmosphere of supportive and helpful feedback, creating a (self-reported) positive impact on postnatal mental health. However, the fact that some women experienced negative feedback led to feelings of motherhood failure on some occasions, and avoidance of posting through fear of negative responses. Conclusion and implications: These findings could inform future decisions made by both parenting website providers and healthcare professionals in making support for mothers more effective and accessible. These may include considerations around the integration of online and offline support services, and the potential increase in trained peer supporters working with mothers

Innate and adaptive autoimmunity in type 1 diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74867/1/j.1399-5448.2007.00334.x.pd

The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype

We previously demonstrated inhibition of ovalbumin (OVA)-induced allergic airway hyper-responsiveness in the mouse using ES-62, a phosphorylcholine-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae. This inhibition correlated with ES-62-induced mast cell desensitisation, although the degree to which this reflected direct targeting of mast cells remained unclear as suppression of the Th2 phenotype of the inflammatory response, as measured by eosinophilia and IL-4 levels in the lungs, was also observed. We now show that inhibition of the lung Th2 phenotype is reflected in ex vivo analyses of draining lymph node recall cultures and accompanied by a decrease in the serum levels of total and OVA-specific IgE. Moreover, ES-62 also suppresses the lung infiltration by neutrophils that is associated with severe asthma and is generally refractory to conventional anti-inflammatory therapies, including steroids. Protection against Th2-associated airway inflammation does not reflect induction of regulatory T cell (Treg) responses (there is no increased IL-10 or Foxp3 expression) but rather a switch in polarisation towards increased T-bet expression and IFNγ production. This ES-62-driven switch in the Th1/Th2 balance is accompanied by decreased IL-17 responses, a finding in line with reports that IFNγ and IL-17 are counter-regulatory. Consistent with ES-62 mediating its effects via IFNγ-mediated suppression of pathogenic Th2/Th17 responses, we found that neutralising anti-IFNγ antibodies blocked protection against airway inflammation in terms of pro-inflammatory cell infiltration, particularly by neutrophils and lung pathology. Collectively, these studies indicate that ES-62, or more likely small molecule analogues, could have therapeutic potential in asthma, in particular for those subtypes of patients (e.g. smokers, steroid-resistant) who are refractory to current treatments

Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy

Helminth parasites such as the nematode Heligmosomoides polygyrus strongly inhibit T helper type 2 (Th2) allergy, as well as colitis and autoimmunity. Here, we show that the soluble excretory/secretory products of H. polygyrus (HES) potently suppress inflammation induced by allergens from the common fungus Alternaria alternata. Alternaria extract, when administered to mice intranasally with ovalbumin (OVA) protein, induces a rapid (1–48 h) innate response while also priming an OVA-specific Th2 response that can be evoked 14 days later by intranasal administration of OVA alone. In this model, HES coadministration with Alternaria/OVA suppressed early IL-33 release, innate lymphoid cell (ILC) production of IL-4, IL-5, and IL-13, and localized eosinophilia. Upon OVA challenge, type 2 ILC (ILC2)/Th2 cytokine production and eosinophilia were diminished in HES-treated mice. HES administration 6 h before Alternaria blocked the allergic response, and its suppressive activity was abolished by heat treatment. Administration of recombinant IL-33 at sensitization with Alternaria/OVA/HES abrogated HES suppression of OVA-specific responses at challenge, indicating that suppression of early Alternaria-induced IL-33 release could be central to the anti-allergic effects of HES. Thus, this helminth parasite targets IL-33 production as part of its armory of suppressive effects, forestalling the development of the type 2 immune response to infection and allergic sensitization

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases