Maternal Schistosomiasis: Immunomodulatory Effects With Lasting Impact on Allergy and Vaccine Responses

Early exposure to immune stimuli, including maternal infection during the perinatal period, is increasingly recognized to affect immune predisposition during later life. This includes exposure to not only viral and bacterial infection but also parasitic helminths which remain widespread. Noted effects of helminth infection, including altered incidence of atopic inflammation and vaccine responsiveness, support further research into the impact these infections have for skewing immune responses. At the same time, despite a sea of recommendations, clear phenotypic and mechanistic understandings of how environmental perturbations in pregnancy and nursing modify immune predisposition and allergy in offspring remain unrefined. Schistosomes, as strong inducers of type 2 immunity embedded in a rich network of regulatory processes, possess strong abilities to shift inflammatory and allergic diseases in infected hosts, for example by generating feedback loops that impair T cell responses to heterologous antigens. Based on the current literature on schistosomiasis, we explore in this review how maternal schistosome infection could drive changes in immune system development of offspring and how this may lead to identifying factors involved in altering responses to vaccination as well as manifestations of immune disorders including allergy

Writing for singing: conceptualising lyric address in contemporary songwriting

© 2015 Dr. Matthew John James LacorciaThis project investigates conceptual approaches to writing popular song lyrics. Through examination of a selection of popular song lyrics from Bette Davis Eyes (Carnes 1981) to Snowflake (Bush 2011), I explore two main textual dimensions: the lyric voice and its act of address; and types of writing such as argumentative discourse, descriptive discourse, and narrative discourse, that are used to structure song lyrics. In doing so, this thesis identifies key tensions in the construction of song lyrics between song as a literal address with fictional features and song as a performance text that is designed to facilitate affective listening experiences for its audience. The creative component of this thesis is a folio of song recordings with lyrics that explore the lyric address, including narrative discourse, argument-driven structures, and unfolding lyric description. These texts attempt to negotiate the writing of a fictive address and creating lyrics that facilitate evocative experiences for listeners

Assessment of serum symmetric dimethylarginine and creatinine concentrations in hyperthyroid cats before and after a fixed dose of orally administered radioiodine

Background: Serum symmetric dimethylarginine (SDMA) is a sensitive renal biomarker for detecting early chronic kidney disease (CKD) in nonhyperthyroid cats, but knowledge regarding its performance in hyperthyroid cats remains limited. Objectives: To determine the relationship between serum SDMA, creatinine and total thyroxine (TT4) concentrations in hyperthyroid cats before (T0) and 3 months after (T1) receiving a PO fixed dose of radioiodine. Animals: Eighty client‐owned hyperthyroid cats. Methods: Prospective cohort study. Serum TT4, and SDMA, creatinine concentrations, and urine specific gravity were measured at T0 and T1. Nonparametric tests were used to determine the relationship among SDMA, and creatinine and TT4 concentrations. Agreement between SDMA and creatinine regarding CKD staging at both time points was assessed using Goodman and Kruskal's gamma statistic. Results: Mean serum SDMA concentration increased after treatment of hyperthyroidism. However, 21 of 75 cats experienced a decrease in SDMA between T0 and T1, whereas creatinine decreased in only 2 cats. A moderate correlation between SDMA and creatinine was seen at T1 (r = 0.53; P < .001) but not at T0 (r = 0.13; P = .25). Where assessable at T1, poor agreement was observed between SDMA and creatinine and CKD stage (Goodman and Kruskal's gamma 0.20; P = .29). Conclusions and clinical importance: Discordant outcomes between SDMA and creatinine after radioiodine treatment in cats with hyperthyroidism suggest extrarenal factors may interfere with the reliability of SDMA to adequately reflect renal function. As a result, SDMA should not be interpreted in isolation in hyperthyroid cats treated with radioiodine

A new standardized treadmill walking test requiring low motor skills in children aged 4-10 years

Exercise intolerance may be reported by parents of young children with respiratory diseases. There is, however, a lack of standardized exercise protocols which allow verification of these reports especially in younger children. Consequently the aims of this pilot study were to develop a standardized treadmill walking test for children aged 4-10 years demanding low sensorimotor skills and achieving high physical exhaustion. In a prospective experimental cross sectional pilot study, 33 healthy Caucasian children were separated into three groups: G1 (4-6 years, n = 10), G2 (7-8 years, n = 12), and G3 (9-10 years, n = 11). Children performed the treadmill walking test with increasing exercise levels up to peak condition with maximal exhaustion. Gas exchange, heart rate, and lactate were measured during the test, spirometry before and after. Parameters were statistically calculated at all exercise levels as well as at 2 and 4 mmol/L lactate level for group differences (Kruskal-Wallis H-test, alpha = 0.05; post hoc: Mann-Whitney U-test with Bonferroni correction alpha = 0.05/n) and test-retest differences (Wilcoxon-rank-sum test) with SPSS. The treadmill walking test could be demonstrated to be feasible with a good repeatability within groups for most of the parameters. All children achieved a high exhaustion level. At peak level under exhaustion condition only the absolute VO2 and VCO2 differed significantly between age groups. In conclusion this newly designed treadmill walking test indicates a good feasibility, safety, and repeatability. It suggests the potential usefulness of exercise capacity monitoring for children aged from early 4 to 10 years. Various applications and test modifications will be investigated in further studies

Clinical safety of percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions in 19 dogs

To evaluate the safety of fine-needle aspiration of adrenal gland lesions in dogs and to characterise the risks in a subset of patients with cytologically or histopathologically diagnosed phaeochromocytoma.Retrospective review of medical records of dogs that underwent percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions between August 2014 and December 2016. Nineteen dogs were identified, with three undergoing bilateral adrenal gland aspiration and one dog undergoing aspiration twice, yielding 23 cytology samples in total. Data collected included signalment, concurrent medical conditions, current medications, blood pressure and heart rate before adrenal fine-needle aspiration, imaging characteristics of the adrenal gland lesions and any clinically apparent procedure-related complications.Phaeochromocytoma was diagnosed in nine of 19 dogs, including one dog with bilateral phaeochromocytoma. One dog developed ventricular tachycardia following aspiration of an adrenal gland lesion cytologically consistent with a phaeochromocytoma.Percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions appears to be relatively safe, even in phaeochromocytoma, but further data are required to lend more weight to this finding. Minimally invasive aspirates could be considered as part of the diagnostic algorithm in the investigation of an incidentally detected adrenal gland lesion of uncertain clinical significance

Host immune responses during Taenia solium Neurocysticercosis infection and treatment.

Taenia solium cysticercosis and taeniasis (TSCT), caused by the tapeworm T. solium, is a foodborne and zoonotic disease classified since 2010 by WHO as a neglected tropical isease. It causes considerable impact on health and economy and is one of the leading causes of acquired epilepsy in most endemic countries of Latin America, Sub-Saharan Africa, and Asia. There is some evidence that the prevalence of TSCT in high-income countries has recently increased, mainly due to immigration from endemic areas. In regions endemic for TSCT, human cysticercosis can manifest clinically as neurocysticercosis (NCC), resulting in epileptic seizures and severe progressive headaches, amongst other neurological signs and/or symptoms. The development of these symptoms results from a complex interplay between anatomical cyst localization, environmental factors, parasite's infective potential, host genetics, and, especially, host immune responses. Treatment of individuals with active NCC (presence of viable cerebral cysts) with anthelmintic drugs together with steroids is usually effective and, in the majority, reduces the number and/or size of cerebral lesions as well as the neurological symptoms. However, in some cases, treatment may profoundly enhance anthelmintic inflammatory responses with ensuing symptoms, which, otherwise, would have remained silent as long as the cysts are viable. This intriguing silencing process is not yet fully understood but may involve active modulation of host responses by cyst-derived immunomodulatory components released directly into the surrounding brain tissue or by the induction of regulatory networks including regulatory T cells (Treg) or regulatory B cells (Breg). These processes might be disturbed once the cysts undergo treatment-induced apoptosis and necrosis or in a coinfection setting such as HIV. Herein, we review the current literature regarding the immunology and pathogenesis of NCC with a highlight on the mobilization of immune cells during human NCC and their interaction with viable and degenerating cysticerci. Moreover, the immunological parameters associated with NCC in people living with HIV/AIDS and treatments are discussed. Eventually, we propose open questions to understand the role of the immune system and its impact in this intriguing host-parasite crosstalk

Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country

Host-parasite interactio

Helminthic dehydrogenase drives PGE2 and IL-10 production in monocytes to potentiate Treg induction.

Immunoregulation of inflammatory, infection-triggered processes in the brain constitutes a central mechanism to control devastating disease manifestations such as epilepsy. Observational studies implicate the viability of Taenia solium cysts as key factor determining severity of neurocysticercosis (NCC), the most common cause of epilepsy, especially in children, in Sub-Saharan Africa. Viable, in contrast to decaying, cysts mostly remain clinically silent by yet unknown mechanisms, potentially involving Tregs in controlling inflammation. Here, we show that glutamate dehydrogenase from viable cysts instructs tolerogenic monocytes to release IL-10 and the lipid mediator PGE2. These act in concert, converting naive CD4+ T cells into CD127−CD25hiFoxP3+CTLA-4+ Tregs, through the G protein-coupled receptors EP2 and EP4 and the IL-10 receptor. Moreover, while viable cyst products strongly upregulate IL-10 and PGE2 transcription in microglia, intravesicular fluid, released during cyst decay, induces pro-inflammatory microglia and TGF-β as potential drivers of epilepsy. Inhibition of PGE2 synthesis and IL-10 signaling prevents Treg induction by viable cyst products. Harnessing the PGE2-IL-10 axis and targeting TGF-ß signaling may offer an important therapeutic strategy in inflammatory epilepsy and NCC