Risk Factors For Q Fever Seroconversion In A Cohort Of Veterinary Students: A Comparative Analysis

Introduction: Coxiella burnetii (C. burnetii) is an extremely infectious, environmentally persistent intracellular bacterium and the causative agent of the zoonosis Q fever. An unprecedented epidemic in the Netherlands between 2007 and 2010 revealed its public health importance. Recent investigations have focused on C. burnetii seroprevalence among livestock workers. The burden of disease in veterinary students, a group with arguably similar exposures, has been insufficiently characterized. Methods: Students beginning veterinary study at Utrecht University\u27s Veterinary Medical School in 2006 were invited to participate. Questionnaires and serum samples for the detection of IgM and IgG antibodies against C. burnetii were collected at baseline and during two follow-up periods. Data was analyzed by the less familiar Random Forest method in addition to classical logistic regression due to the underlying assumptions of generalized linear models that may not be appropriate in this case. Results: During the four-year study period, 19.4% of veterinary students seroconverted. None reported experiencing symptoms. Regression results found students who recently lived on a farm were 5.9 times as likely to seroconvert, and those who completed both the pain management and pre/postnatal care of sheep and lambs elective courses were 9.3 times as likely to seroconvert. Random forest confirmed the regression model\u27s findings and identified male gender as an additional risk factor. Discussion: Students\u27 seroconversion rates were comparable to studies in high-risk occupational groups. Assuming veterinary students are generally subject to chronic, low-intensity exposures, these findings supporting the existing hypothesis that inoculum size determines the severity of acute Q fever. As asymptomatic acute Q fever may progress to symptomatic chronic Q fever, targeted education, surveillance, and vaccination programs should be reconsidered

Subacute sclerosing panencephalitis, a measles complication, in an internationally adopted child.

A healthy 13-year-old boy who had spent the first 4.5 years of his life in an orphanage in Thailand before adoption by an American couple became ill with subacute sclerosing panencephalitis and died several months later. The boy had most likely contracted wild-type measles in Thailand. Measles complications are a risk in international adoptions

Congenital Viral Infections of the Brain: Lessons Learned from Lymphocytic Choriomeningitis Virus in the Neonatal Rat

The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV) infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region–virus–immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV induces delayed-onset neuronal loss after the virus has been cleared, the neonatal rat infected with LCMV may be an excellent model system to study neurodegenerative or psychiatric diseases whose etiologies are hypothesized to be virus-induced, such as autism, schizophrenia, and temporal lobe epilepsy

Host Range and Genetic Diversity of Arenaviruses in Rodents, United Kingdom

During a study to extend our knowledge of the host range and genetic diversity of arenaviruses in Great Britain, 66 of 1,147 rodent blood samples tested for antibody, and 127 of 482 tested by PCR, were found positive. All sequences most closely resembled those of previously identified lymphocytic choriomeningitis virus

Examination of age-dependent effects of fetal ethanol exposure on behavior, hippocampal cell counts, and doublecortin immunoreactivity in rats

WOS: 000333998100002PubMed ID: 24302592Ethanol is known as a potent teratogen having adverse effects on brain and behavior. However, some of the behavioral deficits caused by fetal alcohol exposure and well expressed in juveniles ameliorate with maturation may suggest some kind of functional recovery occurring during postnatal development. The aim of this study was to reexamine age-dependent behavioral impairments in fetal-alcohol rats and to investigate the changes in neurogenesis and gross morphology of the hippocampus during a protracted postnatal period searching for developmental deficits and/or delays that would correlate with behavioral impairments in juveniles and for potential compensatory processes responsible for their amelioration in adults. Ethanol was delivered to the pregnant dams by intragastric intubation throughout 7-21 gestation days at daily dose of 6 g/kg. Isocaloric intubation and intact control groups were included. Locomotor activity, anxiety, and spatial learning tasks were applied to juvenile and young-adult rats from all groups. Unbiased stereological estimates of hippocampal volumes, the total number of pyramidal and granular cells, and double cortin expressing neurons were carried out for postnatal days (PDs) PD1, PD10, PD30, and PD60. Alcohol insult during second trimester equivalent caused significant deficits in the spatial learning in juvenile rats; however, its effect on hippocampal morphology was limited to a marginally lower number of granular cells in dentate gyrus (DG) on PD30. Thus, initial behavioral deficits and the following functional recovery in fetal-alcohol subjects may be due to more subtle plastic changes within the hippocampal formation but also in other structures of the extended hippocampal circuit. Further investigation is required. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 498-513, 2014METU Scientific Research Fund; Turkish Scientific and Technical Council (TUBITAK) [SBAG-107S069]; TUBITAK PhD scholarshipTurkish Scientific and Technical Council (TUBITAK) [SBAG-107S069]Contract grant sponsor: METU Scientific Research Fund.; Contract grant sponsor: Turkish Scientific and Technical Council (TUBITAK); contract grant number: SBAG-107S069 (to E.J.D.).; Contract grant sponsor: TUBITAK PhD scholarship (to B.E.C.)

Increased Seizure Susceptibility and Up-regulation of nNOS Expression in Hippocampus Following Recurrent Early-life Seizures in Rats

This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method. Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4±2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis

Induction of Toll-Like Receptor 3-Mediated Immunity during Gestation Inhibits Cortical Neurogenesis and Causes Behavioral Disturbances

Maternal infection during pregnancy with a wide range of RNA and DNA viruses is associated with increased risk for schizophrenia and autism in their offspring. A common feature in these exposures is that virus replication induces innate immunity through interaction with Toll-like receptors (TLRs). We employed a mouse model wherein pregnant mice were exposed to polyinosinic-polycytidylic acid [poly(I  ⋅  C)], a synthetic, double-stranded RNA molecular mimic of replicating virus. Poly(I ⋅ C) inhibited embryonic neuronal stem cell replication and population of the superficial layers of the neocortex by neurons. Poly(I ⋅ C) also led to impaired neonatal locomotor development and abnormal sensorimotor gating responses in adult offspring. Using Toll-like receptor 3 (TLR3)-deficient mice, we established that these effects were dependent on TLR3. Inhibition of stem cell proliferation was also abrogated by pretreatment with the nonsteroidal anti-inflammatory drug (NSAID) carprofen, a cyclooxygenase (COX) inhibitor. Our findings provide insights into mechanisms by which maternal infection can induce subtle neuropathology and behavioral dysfunction, and they may suggest strategies for reducing the risk of neuropsychiatric disorders subsequent to prenatal exposures to pathogens and other triggers of innate immunity

Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain

BACKGROUND: Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occuring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration. METHODS AND FINDINGS: P7 mice were treated with a single dose of ethanol (5g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot ( n = 4–7/group). Density of Fluoro-Jade B–positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus ( n = 5–6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice ( n = 31–34/group). Nicotinamide reduced the activation of caspase-3 (85.14 ± 4.1%) and the release of cytochrome-c (80.78 ± 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice. CONCLUSIONS: Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS

Persistent Deficits in Heart Rate Response Habituation Following Neonatal Binge Ethanol Exposure

Background: We have previously shown that the rate of habituation of the heart rate orienting response to a novel odor in rats is negatively affected by neonatal ethanol exposure. Thus far, however, only young rats (16 days of age) have been tested. Given the persistence of attention and memory problems evident in humans exposed to ethanol in utero, the purpose of this experiment was to examine the longer-term consequences of ethanol exposure on response habituation. Methods: Ethanol (5.25 g/kg/d) was administered intragastrically to male and female Sprague-Dawley rats on postnatal days (PD) 4 to 9, and controls were given sham intubations. Animals were tested for heart rate orienting and response habituation to a novel olfactory stimulus (amyl acetate) on PD 16, 23, or 30. Results: Animals tested on PD 16 or 23 showed normal heart rate deceleration to the novel odor, a measure of the orienting response. However, ethanol-treated subjects showed impaired response habituation compared with sham controls. While controls exhibited complete habituation within 4 to 5 trials, ethanol-treated animals continued to respond throughout the testing session, with little decrement in heart rate response magnitude across 10 stimulus presentations. A different pattern of responding was observed in animals tested during adolescence (PD 30). Control animals failed to show the typical heart rate decrease indicative of orienting, and instead showed a tendency toward tachycardia. In contrast, ethanol-treated animals tested on PD 30 showed orienting bradycardia that persisted for several trials. Conclusions: These data suggest that there are relatively long-term consequences of neonatal ethanol exposure on nonassociative memory. This impairment in habituation may be relevant to the distractibility and poor focused attention that is pervasive among humans diagnosed with fetal alcohol spectrum disorders