Lyme Borreliosis During Pregnancy

One of the authors (AL) presented a poster on 34 pregnancies of maternal Lyme borreliosis (Lb) in 1995. It was striking that untreated Lb associated with higher probability of adverse outcome but the number of patients were small and the statistical power was low. We have recently published a paper on 95 maternal Lb and the outcome of their pregnancies. Since the closure of the database for that manuscript the number of the pregnant women with Borrelia infection observed in our Centre increased to 124, and the statistical analysis strengthened our previous doubtful observations and reached significant results in important aspects by now. This series is the largest study to date on this topic. Treatment was administered parenterally to 87 (70%) women and orally to 25 (20.0%). Infection remained untreated in 12 (10%) pregnancies. Adverse outcomes were seen in 7/87 (8%), 9/25 (36%), 8/12 (67%), of the parenterally, orally treated and untreated women, respectively. In comparison to patients treated with antibiotics, untreated women had a significantly higher risk of adverse pregnancy outcomes (OR: 11.62, p<0.001). Mothers treated orally comparing to iv. treatment had an increased chance (OR: 6.28) to have an adverse outcome (p=0.001). In the adverse pregnancy outcome, the most impressive difference was between the untreated and parenterally treated women (OR: 21.44, p<0.001). The probability of adverse outcome increased by the exposition time (from the first maternal symptom to the treatment or delivery). When the exposition time has reached four months, the probability of adverse outcome increased by 33%. We had no chance to examine the bacterial invasion of the foetus. Loss of the pregnancy (N=9), small for gestational age or preterm birth (N=7) were the most prevalent adverse outcomes in our series. The other complications were heterogeneous. Our results indicate that untreated or orally treated maternal Borrelia burgdorferi s.l. infection is associated with adverse outcomes. 'Congenital Lyme disease' similar to the Hutchinson's triad in syphilis is unlikely.
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AGMAAS: a GIS integrated tool for modelling wind-borne spreading of FMD virus

The aim of our work was to develop a tool integrated into Quantum GIS (QGIS) that can help
the user estimate and visualize the possible infective areas around an outbreak based on HYbrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model

Survey of lungworm infection of domestic cats in Hungary

From 61 settlements of 12 Hungarian counties, 303 domestic cats were included in this survey. Between autumn 2016 and spring 2018, fresh faecal samples were randomly collected and examined by flotation and by the Baermann–Wetzel method for the presence of lungworm infection. No eggs of Eucoleus aerophilus were detected. Morphological identification of first instar larvae (L1) was also carried out. In the faeces of 60 cats (19.8%) from 17 settlements and Budapest, L1 of Aelurostrongylus abstrusus were found. More than half of the cats were from the western part of the country. The average number of larvae per gram of faeces was 190.2 ± 304.88. These results are in line with the former findings on the prevalence of aelurostrongylosis of domestic cats in Hungary. In addition, Oslerus rostratus was also found for the first time in the faecal samples of three cats from the eastern part of the country, infected also with Ae. abstrusus. The average age (2.51 ± 1.26 years) of infected cats indicates that lungworm infection is more common among younger cats. No relationship was found between the lung-worm infection and the sex of cats. Non-neutered cats had a significantly higher proportion of lungworm infections. Two-thirds of the infected cats were apparently healthy, and only 19 individuals showed clinical signs of respiratory disorders

A gazda-parazita kapcsolat evolúciós-ökológiai vizsgálata = Evolutionary ecological studies on the host-parasite relationship

Pályázatunk munkaterve mozaikos felépítésű volt, több, egymáshoz is kapcsolódó, de mégis megkülönböztethető résztémát ölelt fel. Valamennyi résztéma a gazda-parazita kapcsolatok és a tágan értelmezett, természettudományos szemléletű epidemiológia kérdéseihez kapcsolódott, és különösen a gazda-parazita kapcsolatok evolúciós, ökológiai és viselkedéstudományi elemzéséhez köthető. Munkáink egy része metodikai fejlesztés volt, ezek eredményei új tudományos szoftverek a parazitológia és a térbeli epidemiológia terén. Más eredményeink új tudományos hipotézisek létrehozását célozták (4 dolgozat). Tanulmányaink a gazda-parazita evolúciós-ökológiai kapcsolatok terén többek közt a madarak ivóz-higiéniai adaptációit és toll-lyukait, valamint a tetvek fajgazdagságát és ivari dimorfizmusát elemezték. Számos dolgozatunk konkrét biológiai-epidemiológiai esettanulmányt foglalt magába (pl. veszettség, kutyák bolha-, kullancs-, Babesia- és Borrelia-fertőzöttsége, őzek papilloma-vírus, madarak Usutu-vírus fertőzöttsége). Két dolgozatunk a biológiai fegyverek történetével és a biológiai biztonsággal foglalkozott. Eredményeinket impaktos lapban publikált mintegy 20 db tanulmányban, illetve számos más hazai és nemzetközi fórumon is közzé tettük. E munkáink egy részét máris citálják az ISI Web of Science-ben. | This research project was based on a mosaic-like research plan consisting of several small subject connected to each other. Each of these was related to biological epidemiology, or - more specifically - to the evolutionary, ecological and behavioural study of pathogens and diseases. Part of our studies were methodological, these mostly resulted in new scientific software. Another type of our results comes in the form of new hypotheses (4 articles). Our studies within the field of the evolution and ecology of host-parasite interactions investigated the drinking-water preferences of birds, the origin of feather holes in small passerines, the taxonomic richness and the sexual size dimorphism of avian lice. Furthermore, we have analysed particular epidemics like rabies, flea, tick, Babesia and Borrelia infections of dogs, the Papilloma virus infections of the roe deer, and the Usutu virus infections of wild birds. Two of our studies examine some aspects of the history of biological warfare. Results of the above studies were published in cca. 20 papers in relevant scientific journals and also at several other Hungarian and international forums, and some of these are already cited in ISI Web of Science

Ovariectomy and Subsequent Treatment with Estrogen Receptor Agonists Tune the Innate Immune System of the Hippocampus in Middle-Aged Female Rats

The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER) agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands), local estradiol synthesis (P450 aromatase) and estrogen reception (ER). Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b) and complement (C3, factor B, properdin) genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a) expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERa gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERa agonist closely resembled those of estradiol, ERb agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu. In ovariectomized female rats, estradiol replacement exerts potent immunomodulatory effects including attenuation of microglia sensitization, initiation of M2-like activation and modulation of complement expression by targeting hippocampal neurons and glial cells through ERa and ERb

Ovariectomy Alters Gene Expression of the Hippocampal Formation in Middle-Aged Rats

Ovarian hormones regulate the transcriptome of the hippocampus and modulate its functions. During 29 menopause, this complex signaling declines, leading to impaired learning and memory. This study was 30 undertaken to clarify the effects of long-term, surgical ovariectomy (OVX) on the rat hippocampal 31 transcriptome. At age of 13 months, intact control and ovariectomized groups were formed. All animals 32 were sacrificed 5 weeks after gonadectomy, hippocampal formations were dissected and processed for 33 transcriptome analysis. Microarray and PCR studies identified 252 and 61 genes, respectively, whose 34 expression was altered in the lack of ovarian hormones. Pathway analysis revealed impact on 35 neuroactive ligand-receptor interaction, endocannabinoid and estrogen signaling, among others. 36 Network and interaction analyses of proteins encoded by OVX-regulated genes revealed upregulation 37 of growth/ troph/transcription factor signaling assembly (Mdk, Fgf1, Igf2, Ngf, Ngfr, Ntf3, Ntrk1, Otx2, 38 Hif1a, Esr1, Nr4a3), peptides/peptide receptors (Cartp, Kl, Ttr, Gnrhr), neurotransmission (Grm1, 39 Gria4, Gls, Slc18a2, Kcj6) and genes serving immune functions (C3, Ccl2, Itgam, Il1b). Downregulated 40 clusters included neuropeptides and their receptors (Adcyap1, Cbln2, Cck, Cckbr, Crhr1 and 2, Oprd1, 41 Nts, Penk, Sstr1, Vip), neurotransmitter signaling (Htr2c, hrna3, Chrm4, Grm8, Hrh3, Slc17a6) and 42 potassium channels (Kcnk9, Kcnj9, Kcnma1, Kcnc2). Several transcription factors (Rxra, Thrb), solute 43 carriers and defense molecules (Apitd1, Bcl2, Clql3, Ilr3a, Sod1, Sncb) also underwent downregulation. 44 The findings indicate that surgical gonadectomy carried out at middle-age robustly changes the 45 hippocampal transcriptome that alters neurogenesis, synaptic plasticity, immune modulation causing 46 cognitive dysfunctions

Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes.

BACKGROUND The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. METHODS We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. RESULTS Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, C3, Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. CONCLUSIONS Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state which can be characterized by up-regulation of CD11b, CD14, CD18, CD45, CD74, CD86, TLR4, down-regulation of CD36 and unchanged CD40 expression. As a result of this shift, microglial cells have lower threshold for subsequent activation in the forebrain of postmenopausal women

Random matrix analysis of localization properties of Gene co-expression network

We analyze gene co-expression network under the random matrix theory framework. The nearest neighbor spacing distribution of the adjacency matrix of this network follows Gaussian orthogonal statistics of random matrix theory (RMT). Spectral rigidity test follows random matrix prediction for a certain range, and deviates after wards. Eigenvector analysis of the network using inverse participation ratio (IPR) suggests that the statistics of bulk of the eigenvalues of network is consistent with those of the real symmetric random matrix, whereas few eigenvalues are localized. Based on these IPR calculations, we can divide eigenvalues in three sets; (A) The non-degenerate part that follows RMT. (B) The non-degenerate part, at both ends and at intermediate eigenvalues, which deviate from RMT and expected to contain information about {\it important nodes} in the network. (C) The degenerate part with $zero$ eigenvalue, which fluctuates around RMT predicted value. We identify nodes corresponding to the dominant modes of the corresponding eigenvectors and analyze their structural properties