Solitary rectal ulcer syndrome (SRUS): observational case series findings on MR defecography

Objective: Radiological findings in solitary rectal ulcer syndrome (SRUS) are well described for evacuation proctography (EP) but sparse for magnetic resonance defecography (MRD). In order to rectify this, we describe the spectrum of MRD findings in patients with histologically proven SRUS. / Materials and methods: MRD from twenty-eight patients (18 female; 10 males) with histologically confirmed SRUS were identified. MRD employed a 1.5-T magnet and a standardized technique with the rectal lumen filled with gel and imaged sagittally in the supine position, before, during, and after attempted rectal evacuation. A single radiologist observer with 5 years’ experience in pelvic floor imaging made the anatomical and functional measurements. / Results: Sixteen patients (10 female) demonstrated internal rectal intussusception and 3 patients (11%) demonstrated complete external rectal prolapse. Anterior rectoceles were noted in 12 female patients (43%). Associated anterior and middle compartment weakness (evidenced by excessive descent) was observed in 18 patients (64%). Cystocele was found in 14 patients (50%) and uterine prolapse was noted in 7 patients (25%). Enterocoeles were detected in 5 patients (18%) and peritoneocoele in 5 patients (18%). None had sigmoidocoele. Sixteen patients (57%) demonstrated delayed voiding and 13 patients (46%) incomplete voiding, suggesting defecatory dyssynergia. / Conclusion: MRD can identify and grade both rectal intussusception and dyssynergia in SRUS, and also depict associated anterior and/or middle compartment descent. Distinction between structural and functional findings has important therapeutic implications. Key Points: MRD can identify and grade both rectal intussusception and dyssynergia in patients with SRUS. MRD is an acceptable substitute to evacuation proctography in assessing anorectal dysfunctions when attempting to avoid ionizing radiation. SRUS influences the pelvic floor globally. MRD depicts associated anterior and/or middle compartment prolapse

The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles.

Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite

HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico

<p>Abstract</p> <p>Background</p> <p>Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (<it>HFE</it>) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight.</p> <p>Methods</p> <p>We investigated the role of <it>HFE C282Y</it>, <it>HFE H63 D</it>, and transferrin <it>(TF) P570 S </it>gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant <it>HFE </it>or <it>TF </it>genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates.</p> <p>Results</p> <p>3.1%, 16.8% and 17.5% of infants (N = 390) and 1.9%, 14.5% and 18.9% of mothers (N = 533) carried the <it>HFE C282Y</it>, <it>HFE H63D</it>, and <it>TF P570 S </it>variants, respectively. The presence of infant <it>HFE H63 D </it>variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal <it>HFE H63 D </it>variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant <it>HFE H63 D </it>genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal <it>HFE H63 D </it>variant carriers had a negative association between tibia lead and birthweight.</p> <p>Conclusions</p> <p>These results suggest that the <it>HFE H63 D </it>genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.</p

Impact of protozoan cell death on parasite-host interactions and pathogenesis

PCD in protozoan parasites has emerged as a fascinating field of parasite biology. This not only relates to the underlying mechanisms and their evolutionary implications but also to the impact on the parasite-host interactions within mammalian hosts and arthropod vectors. During recent years, common functions of apoptosis and autophagy in protozoa and during parasitic infections have emerged. Here, we review how distinct cell death pathways in Trypanosoma, Leishmania, Plasmodium or Toxoplasma may contribute to regulation of parasite cell densities in vectors and mammalian hosts, to differentiation of parasites, to stress responses, and to modulation of the host immunity. The examples provided indicate crucial roles of PCD in parasite biology. The existence of PCD pathways in these organisms and the identification as being critical for parasite biology and parasite-host interactions could serve as a basis for developing new anti-parasitic drugs that take advantage of these pathways

Semiochemical-based alternatives to synthetic toxicant insecticides for pollen beetle management

There is an urgent need to develop sustainable pest management systems to protect arable crops in order to replace the current over-reliance on synthetic insecticides. Semiochemicals are insect- or plant-derived chemicals that are used by organisms as information signals. Integrated pest management tools are currently in development that utilise semiochemicals to manipulate the behaviour of pest insects and their natural enemies to provide effective control of pests within the crop. These innovative tools usually require fewer inputs and can involve multiple elements therefore reducing the likelihood of resistance developing compared with use of synthetic toxicants. We review here the life cycle of the pollen beetle Brassicogethes aeneus (previously known as Meligethes aeneus) which is a pest insect of oilseed rape (Brassica napus) and describe the current knowledge of any behaviour mediated by semiochemicals in this species. We discuss the behavioural processes where semiochemical-based control approaches may be appropriate and consider how these approaches could be integrated into an integrated pest management strategy for this important arable crop

Role of Temperature in the Growth of Silver Nanoparticles Through a Synergetic Reduction Approach

This study presents the role of reaction temperature in the formation and growth of silver nanoparticles through a synergetic reduction approach using two or three reducing agents simultaneously. By this approach, the shape-/size-controlled silver nanoparticles (plates and spheres) can be generated under mild conditions. It was found that the reaction temperature could play a key role in particle growth and shape/size control, especially for silver nanoplates. These nanoplates could exhibit an intensive surface plasmon resonance in the wavelength range of 700–1,400 nm in the UV–vis spectrum depending upon their shapes and sizes, which make them useful for optical applications, such as optical probes, ionic sensing, and biochemical sensors. A detailed analysis conducted in this study clearly shows that the reaction temperature can greatly influence reaction rate, and hence the particle characteristics. The findings would be useful for optimization of experimental parameters for shape-controlled synthesis of other metallic nanoparticles (e.g., Au, Cu, Pt, and Pd) with desirable functional properties

Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic Backgrounds

The single-celled parasite Leishmania, transmitted by sand flies in more than 88 tropical and sub-tropical countries globally, infects man and other mammals, causing a spectrum of diseases called the leishmaniases. Over 12 million people are currently infected worldwide with 2 million new cases reported each year. The type of leishmaniasis that develops in the mammalian host is dependent on the species of infecting parasite and the immune response to infection (that can be influenced by host genetic variation). Our research is focused on identifying parasite factors that contribute to pathogenicity in the host and understanding how these might differ between parasite species that give rise to the different clinical forms of leishmaniasis. Molecules of this type might lead to new therapeutic tools in the longer term. In this paper, we report a comparative analysis of gene expression profiles in three Leishmania species that give rise to different types of disease, focusing on the intracellular stages that reside in mammalian macrophages. Our results show that there are only a small number of differences between these parasite species, with host genetics playing only a minor role in influencing the parasites' response to their intracellular habitat. These small changes may be significant, however, in determining the clinical outcome of infection

Draft Genome Sequencing of Giardia intestinalis Assemblage B Isolate GS: Is Human Giardiasis Caused by Two Different Species?

Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life