A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background
Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.

Methods
The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.

Results
Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

Conclusions
Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Managing the risks from new and emerging infectious disease: the 'one health' paradigm

The global risk from new and emerging infectious diseases continues to grow with recognition that, for the most part, the pathogens involved emerge from animals to infect humans. Recognizing the complexity of these interactions and the need for a strong interdisciplinary approach to effectively manage these risks, new partnerships are being forged under the general umbrella of 'one health'. Involving human health, animal health, and environmental health exponents, solutions are sought for how to prevent as well as respond to the threats. But is this approach working? Whilst a number of key meetings continue to be held under the One Health umbrella, are we really seeing measureable progress in risk prevention and mitigation? Focusing research on the drivers for emergence, on modeling the risks, on improved diagnostics, and on targeted vaccines could considerably enhance our ability to prevent and respond. Ensuring the uptake and applications of new diagnostics and vaccines will be the key to prevention and response, but achieving this will require policies that drive further the One Health collaborations. Such policies should ensure that scant available resources are targeted toward the identified outcomes through research delivery and uptake, and that we genuinely work as "one world" in tackling the very real risks we face

Fishy business : effect of omega-3 fatty acids on zinc transporters and free zinc availability in human neuronal cells

Omega-3 (ω-3) fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA). The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer's disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s) for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.

Phylogenetic analysis of beak and feather disease virus across a host ring-species complex

Pathogens have been hypothesized to play a major role in host diversity and speciation. Susceptibility of hybrid hosts to pathogens is thought to be a common phenomenon that could promote host population divergence and subsequently speciation. However, few studies have tested for pathogen infection across animal hybrid zones while testing for codivergence of the pathogens in the hybridizing host complex. Over 8 y, we studied natural infection by a rapidly evolving single-strand DNA virus, beak and feather diseases virus (BFDV), which infects parrots, exploiting a host-ring species complex (Platycercus elegans) in Australia. We found that host subspecies and their hybrids varied strikingly in both BFDV prevalence and load: both hybrid and phenotypically intermediate subspecies had lower prevalence and load compared with parental subspecies, while controlling for host age, sex, longitude and latitude, as well as temporal effects. We sequenced viral isolates throughout the range, which revealed patterns of genomic variation analogous to Mayr's ring-species hypothesis, to our knowledge for the first time in any host-pathogen system. Viral phylogeny, geographic location, intraspecific host density, and parrot community diversity and composition did not explain the differences in BFDV prevalence or load between subpopulations. Overall, our analyses suggest that functional host responses to infection, or force of infection, differ between subspecies and hybrids. Our findings highlight the role of host hybridization and clines in altering host-pathogen interactions, dynamics that can have important implications for models of speciation with gene flow, and offer insights into how pathogens may adapt to diverging host populations.

Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells

In the current study, the relative contribution of cell-surface components (CSC) and cell-free supernatants (CFS) in the immuno-modulatory properties of 17 strains of probiotic and lactic acid bacteria (LAB) was assessed. The production of pro- and antiinflammatory cytokines including IL-2, IL-4, IL-10, IL-12 p70, IFN-γ, tumor necrosis factor-α (TNF-α), and transforming growth factor-β was measured at different time points after stimulation of buffy coat derived-peripheral blood mononuclear cells (PBMC) from healthy donors with CSC and CFS of probiotic and LAB. Results showed that CSC of probiotic and LAB strains induced production of T helper 1 and 2 type cytokines. Transforming growth factor-β was stimulated at highest concentrations, followed by IL-10 and TNF-α. The CFS of all tested bacterial strains induced PBMC for significantly high levels of IL-10 secretion compared with unstimulated cells, but the values were less than lipopolysaccharide-stimulated cells. Cytokines due to CFS stimulation showed declined concentration for IL-2, TNF-α, and IL-4, and complete disappearance of IL-12, IFN-γ, and transforming growth factor-β in the cultured medium at 96 h of incubation. Results of cytokine data demonstrate proinflammatory TNF-α immune responses are mainly directed through cell-surface structures of probiotic and LAB, but antiinflammatory immune responses are mediated both by metabolites and cell-surfaces of these bacteria. The induction of CD4(+)CD25(+) regulatory T cells after stimulation of PBMC with CSC and CFS of probiotic and LAB showed regulatory T cell activity appeared to be influenced both by the CSC and metabolites, but was principally triggered by cell surfaces of probiotic and LAB strains.

Heterogeneous copper concentrations in cancerous human prostate tissues

© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Background Therapeutics that target copper for the treatment of prostate cancer are being evaluated in human clinical trials. Elevated intracellular copper is considered to sensitize prostate cancer cells to certain copper-coordination compounds, especially those with ionophoric properties. While there is compelling in vitro evidence that prostate cancer cells accumulate intracellular copper, a corresponding status for copper in patient tissues has not been corroborated. We therefore established whether copper concentrations increase in cancerous prostate tissues, and in sera, in patients throughout disease progression. Methods Human prostate tissue samples were obtained from patient prostatectomies (n=28), and together with patient-matched sera, were analyzed for copper content by inductively coupled plasma mass spectrometry. Results When grouped together, cancerous prostate tissues exhibiting moderate disease severity (Gleason Score 7) (n=10) had 1.6-fold more copper than age-matched normal tissues (n=10) (P<0.05). Those with more aggressive disease (Gleason Score 9) (n=8) had 1.8-fold more copper (P<0.05). In both disease stages however, the copper concentrations between individual samples were rather variable (0.55-3.02μg/g), with many clearly within the normal range (0.52-1.28μg/g). Additionally, we found that there was no change in serum copper concentrations in patients with either moderate or aggressive prostate cancer (Gleason Score 7 or 9), compared with reference intervals and to age-matched controls. Conclusions The heterogeneous nature of copper concentrations in cancerous prostate tissues, suggest that a small subset of patients may respond to treatments that target elevated intratumoral copper. Therefore, such approaches would likely require personalized treatment strategies. Prostate 75:1510-1517, 2015.

Sources of human non-typhoid salmonellosis: a review

Salmonellosis is a worldwide disease caused by bacteria of the genus Salmonella. Currently, there are over 2,500 identified serovars of Salmonella. A reduced number of these serovars, about eighty, are implicated in most animals and human diseases. Most cases of salmonellosis in humans are associated with the consumption of contaminated food products such as beef, pork, poultry meat, eggs, vegetables, juices and other kind of foods. It may also be associated with the contact between humans and infected pet animals. Therefore, the chain of human salmonellosis is very complex and in most cases the origin of the infection is difficult to establish. The use of antimicrobial agents to treat and to prevent bacterial infections in humans and animals, as well as as growth promoters in animal production, has favoured the selection and transference of resistance genes between different bacteria, including Salmonella serovars. Many studies have confirmed the role of foods of animal origin as a source of multi drugresistant Salmonella serovars. For this reason, continuous surveillance of these pathogens along the food chain together with the responsible use of antimicrobial agents is necessary.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45(51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.

The first reported case of human tick paralysis in Brazil: a new induction pattern by immature stages

Tick paralysis (TP) is a rare disease with rapid progression and potential fatal evolution. Immediately after the diagnosis, removal of all ticks from the body of the patient is mandatory. The present study reports for the first time a human case of the disease in Brazil. The patient had loss of muscle strength, decreased reflexes and marked palpebral ptosis. Six hours after removal of the last tick, the ptosis improved and on the following day, the patient had near total regression of the symptoms. This report emphasizes the possible presence of similar cases that should be promptly diagnosed and quickly treated. A new induction pattern for TP in humans associated with immature stages of ticks is also presented.

Morphological and molecular characterization of an equine isolate of Pythium insidiosum and comparison with the first human isolate from the same geographic region

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Paracoccidioides brasifiensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P brasiliensis killing by human PMNs, and that H2O2 and Superoxide anion participate as effectors molecules in this process.

Retrospective analysis of post-exposure to human anti-rabies treatment in Botucatu, São Paulo State, Brazil

This analysis aimed to identify characteristics of accidents that would, probably, provoke rabies infection. A total of 14,409 survey questionnaires for surveillance of human rabies from the Brazilian Information System for Disease Notification (SINAN), from 2000 to 2005, were analyzed. Regarding demographics, it was observed that 7,377 (51.5%) of the victims were white, 4,458 (30.93%) were children and 8,008 (55.58%) were males. Urban cases were prevalent (88.10%) while dogs were the animals most frequently involved in accidents, in 11,700 cases (81.19%). Bites (84.35%) and scratches (19.15%) were the most prevalent exposure types, and occurred predominantly on victims' extremities (38.79%). The prophylactic measure taken in 6,179 cases comprised anti-rabies vaccine; of these victims, 421 (2.92%) showed systemic reactions while 693 (4.80%) reported no response. The importance of developing awareness in professionals that should correctly report post-exposure immunoprophylaxis cases is emphasized given the high number of individuals who receive this type of treatment annually.