Search

IntroductionTularemia is mainly caused by Francisella tularensis (Ft) subsp. tularensis (Ftt) and Ft subsp. holarctica (Ftt) in humans and in more than 200 animal species including rabbits and hares. Human clinical manifestations depend on the route of infection and range from flu-like symptoms to severe pneumonia with a mortality rate up to 60% without treatment. So far, only 2D cell culture and animal models are used to study Francisella virulence, but the gained results are transferable to human infections only to a certain extent.MethodIn this study, we firstly established an ex vivo human lung tissue infection model using different Francisella strains: Ftt Life Vaccine Strain (LVS), Ftt LVS ΔiglC, Ftt human clinical isolate A-660 and a German environmental Francisella species strain W12-1067 (F-W12). Human lung tissue was used to determine the colony forming units and to detect infected cell types by using spectral immunofluorescence and electron microscopy. Chemokine and cytokine levels were measured in culture supernatants.ResultsOnly LVS and A-660 were able to grow within the human lung explants, whereas LVS ΔiglC and F-W12 did not replicate. Using human lung tissue, we observed a greater increase of bacterial load per explant for patient isolate A-660 compared to LVS, whereas a similar replication of both strains was observed in cell culture models with human macrophages. Alveolar macrophages were mainly infected in human lung tissue, but Ftt was also sporadically detected within white blood cells. Although Ftt replicated within lung tissue, an overall low induction of pro-inflammatory cytokines and chemokines was observed. A-660-infected lung explants secreted slightly less of IL-1β, MCP-1, IP-10 and IL-6 compared to Ftt LVS-infected explants, suggesting a more repressed immune response for patient isolate A-660. When LVS and A-660 were used for simultaneous co-infections, only the ex vivo model reflected the less virulent phenotype of LVS, as it was outcompeted by A-660.ConclusionWe successfully implemented an ex vivo infection model using human lung tissue for Francisella. The model delivers considerable advantages and is able to discriminate virulent Francisella from less- or non-virulent strains and can be used to investigate the role of specific virulence factors.

Abstract The Borna disease virus 1 (BoDV-1) causes severe and often fatal encephalitis in humans. The virus is endemic in parts of Germany, Liechtenstein, Switzerland and Austria. As an increasing number of human BoDV-1 encephalitis cases is being diagnosed, the chance for healthcare professionals to come into contact with infected tissues and bodily fluids from patients with known acute bornavirus encephalitis is also increasing. Therefore, risk assessments are needed. Based on three different incidences of possible exposure to BoDV-1 including an autopsy knife injury, a needlestick injury, and a spill accident with cerebrospinal fluid from patients with acute BoDV-1 encephalitis, we perform risk assessments and review published data. BoDV-1 infection status of the index patient’s tissues and bodily fluids to which contact had occurred should be determined. There is only scarce evidence for possible postexposure prophylaxis, serology, and imaging in healthcare professionals who possibly came into contact with the virus. Despite decade-long laboratory work with BoDV-1, not a single clinically apparent laboratory infection has been published. Given the increasing number of severe or fatal BoDV-1 encephalitis cases, there is a growing need for efficacy-tested, potent antiviral therapeutics against BoDV-1 in humans, both in clinically ill patients and possibly as postexposure prophylaxis in healthcare professionals.

The 1914 uprising of Sam Neua (Houaphan Province, NE Laos) laid bare complex processes of social and economic mobilization in the mountainous hinterlands of French Indochina. As a first prelude to the upcoming anticolonial struggles in the Lao-Vietnamese borderlands, this heterogeneous movement is only little understood in its sociopolitical and cultural dimensions. Though initiated by armed Chinese bands, the participation of different upland ethnic groups suggests that the uprising was also the result of socioeconomic discontent and disquiet among the local population. At the beginning of the twentieth century, colonial interventions in upland Laos unsettled economic and political configurations, and confronted local powerbrokers with both restrictions and new opportunities. Colonial infrastructure development negatively affected Chinese trade and mobility in northern Indochina – a key factor for the escalation in Sam Neua. By means of combining microhistory and historical anthropology, this paper aims to investigate forms of mobility, mimetic encounters, and shifting conceptions of sociopolitical hierarchies in colonial Indochina that have so far received only scant attention. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore individual predictors of support for peace agreements after their implementation. The aim is to test if individual differences in Social Dominance Orientation (SDO) temper the effect of exposure to violence on support for peace agreements. One hundred and eighty participants completed measures surveying their SDO, exposure to violence and voting behavior four years after the peace agreement between the Colombian government and the FARC in 2016. Results show that SDO lowers support for the peace agreement four years after it was signed among those who experienced violence but has a smaller effect on those who did not experience violence. The implications of the interaction between SDO and exposure to violence are discussed. [ABSTRACT FROM AUTHOR]

Investigating nocifensive withdrawal reflexes as potential surrogate marker for the spinal excitation level may widen the understanding of maladaptive nociceptive processing after spinal cord injury (SCI). The aim of this prospective, explorative cross-sectional observational study was to investigate the response behavior of individuals with SCI to noxious radiant heat (laser) stimuli and to assess its relation to spasticity and neuropathic pain, two clinical consequences of spinal hyperexcitability/spinal disinhibition. Laser stimuli were applied at the sole and dorsum of the foot and below the fibula head. Corresponding reflexes were electromyography (EMG) recorded ipsilateral. Motor responses to laser stimuli were analyzed and related to clinical readouts (severity of injury/spasticity/pain), using established clinical assessment tools. Twenty-seven participants, 15 with SCI (age 18–63; 6.5 years post-injury; AIS-A through D) and 12 non-disabled controls, [non-disabled controls (NDC); age 19–63] were included. The percentage of individuals with SCI responding to stimuli (70–77%; p < 0.001), their response rates (16–21%; p < 0.05) and their reflex magnitude (p < 0.05) were significantly higher compared to NDC. SCI-related reflexes clustered in two time-windows, indicating involvement of both A-delta- and C-fibers. Spasticity was associated with facilitated reflexes in SCI (Kendall-tau-b p ≤ 0.05) and inversely associated with the occurrence/severity of neuropathic pain (Fisher’s exact p < 0.05; Eta-coefficient p < 0.05). However, neuropathic pain was not related to reflex behavior. Altogether, we found a bi-component motor hyperresponsiveness of SCI to noxious heat, which correlated with spasticity, but not neuropathic pain. Laser-evoked withdrawal reflexes may become a suitable outcome parameter to explore maladaptive spinal circuitries in SCI and to assess the effect of targeted treatment strategies. Registration: https://drks.de/search/de/trial/DRKS00006779.

Background: Many school health teacher preparation programs do not train teacher candidates in the use of online resources available through the Centers for Disease Control and Prevention (CDC). Some CDC resources, such as the School Health Index, could significantly improve the quality of school health programs. To address this, the CDC and the American Cancer Society collaborated to train school health faculty to integrate these resources into teacher preparation programs. Purpose: This study evaluated the effect of the Institutes for Higher Education Academy (IHEA), a professional conference intended to train school health faculty in the use of the CDC online resources and to facilitate resource integration into health teacher preparation. Methods: This mixed methods study had two data collection phases. The quantitative phase used an online survey to determine the number of changes made in participants' programs. All school health faculty members who attended an IHEA were recruited via e-mail to participate (N = 151). After three rounds of reminder e-mails, an acceptable participation rate was reached (68%). Descriptive statistics and inferential statistics (Pearson correlations) were used to analyze data. In the qualitative phase, all participants who completed the survey were recruited to complete a follow-up phone interview (n = 103).The interview was tailored to each participant based upon survey responses to elicit examples of program changes made as a result of IHEA attendance, as well as benefits and barriers to change. Fifty-four interviews were conducted and recorded, then transcribed and coded. An inter-rater coded 15% of the transcripts to ensure inter-rater reliability. Qualitative data were triangulated with participant survey data. Results: The majority of IHEA attendees surveyed made changes to their teacher preparation programs, and subsequently trained an estimated 2,800 pre-service school health educators to use the CDC online resources. Through participant outreach, more than 7,000 school health faculty and in-service K-12 health educators were also trained. Conclusions: IHEA is an effective and sustainable approach to improving the quality of K-12 school health education.

Even after decades of research and pharmaceutical development, cancer is still one of the most common causes of death in the western population and the management of cancer will remain a major challenge of medical research. One of the most common types of cancer is colorectal cancer (CRC). Prevention by detection of early-stage precursors is the most reliable method to prevent CRC development. In dependence of age, familial predisposition, and other risk factors the preventative routine screening for CRC by colonoscopy should be performed at least twice in intervals of about ten years. Although colonoscopy is a life-saving clinical examination reducing both incidence and mortality of CRC significantly, it has still a bad reputation in the population as an uncomfortable procedure with unpleasant side effects lasting sometimes over days to weeks. These effects are most likely caused by the bowel preparation before colonoscopy, which is crucial for a successful colonoscopy with high quality. Beside pain, bleeding and other rare but severe complications of colonoscopy, cleaning of the intestinal mucosa alters the gut microbiome significantly and consistently. Abdominal pain, cramps, diarrhea, nausea, bloating, and constipation are common adverse events which can continue to affect patients for days or even weeks after the procedure. In this multicenter, placebo controlled, double blind clinical trial, we investigated the effect of an intervention with a multispecies probiotic formulation for 30 days on the adverse events due to bowel preparation. We show that the treatment of participants with the multispecies probiotic formulation decreases the number of days with constipation significantly, and reduced pain, bloating, diarrhea, and general discomfort. 16S based amplicon analyses reveal recovery of administered probiotic strains from stool samples and differences in alpha diversity dynamics with higher variability in the probiotic group compared to the placebo group. In conclusion, the probiotic ameliorates the side effects after colonoscopy and might be an important supplement to increase acceptance of this life-saving preventative examination. Further, we present here for the first time that probiotic intervention of only 30 days affects alpha diversity parameters in stool samples.

Fluctuating lesions or furuncles of the scalp occur frequently in dermatological practice. This clinical condition is often caused by gram positive bacteria (e.g. staphylococcal or streptococcal skin infection) or fungal infection (e.g. Kerion celsi). However, a rare diagnosis such as myiasis might be considered, especially if a journey to an endemic area is reported. Herein, we present a case of furunculoid myiasis of the scalp and review the pathogenesis and therapeutic options to treat this condition.

Abstract Background The true burden and geographical distribution of human Borna disease virus 1 (BoDV-1) encephalitis is unknown. All detected cases so far have been recorded in Bavaria, southern Germany. Case presentation A retrospective laboratory and epidemiological investigation of a 2017 case of fatal encephalitis in a farmer in Brandenburg, northeast Germany, demonstrated BoDV-1 as causative agent by polymerase chain reaction, immunohistochemistry and in situ hybridization. Next-generation sequencing showed that the virus belonged to a cluster not known to be endemic in Brandenburg. The investigation was triggered by a recent outbreak of animal Borna disease in the region. Multiple possible exposures were identified. The next-of-kin were seronegative. Conclusions The investigation highlights clinical awareness for human BoDV-1 encephalitis which should be extended to all areas endemic for animal Borna disease. All previously diagnosed human cases had occurred > 350 km further south. Further testing of shrews and livestock with Borna disease may show whether this BoDV-1 cluster is additionally endemic in the northwest of Brandenburg.

Human subcutaneous dirofilariasis is an emerging mosquitoborne zoonosis. A traveler returning to Germany from India experienced Dirofilaria infection with concomitant microfilaremia. Molecular analysis indicated Dirofilaria repens nematodes of an Asian genotype. Microfilaremia showed no clear periodicity. Presence of Wolbachia endosymbionts enabled successful treatment with doxycycline.

Background: Alveolar echinococcosis (AE) is a severe larval tapeworm infection with a variable clinical course of the disease. Reliable imaging techniques and biomarkers are needed to predict the course of the disease. Methods: 179 AE patients that received PET/CT scans between 2008 and 2012 were retrospectively included. From stored blood samples taken on the day of the scan, levels of IgE, parasite-specific serology, amyloid A, C-reactive protein, soluble interleukin 2 receptor, cytokeratin fragments, eosinophilic cell count, and eosinophil cationic protein were measured. Additionally, the current clinical outcome (cured, stable, or progressive disease) after a median duration of 8 years after baseline examination was assessed. Ultimately, an ordinal logistic regression was conducted to evaluate which imaging parameters and biomarkers independently influence the clinical outcome. Results: In general, patients in need of medical treatment or with progressive disease, advanced PNM stages, and positive PET/CT scans exhibited higher levels of the respective biomarkers. However, only the parasite-specific serological markers and total IgE levels differed significantly between clinical groups, WHO PNM stages, and the results of the PET/CT scan. In the multivariate analysis, PET/CT results were a strong predictor of the clinical outcome (OR 8.908, 95%CI 3.019–26.285; p < 0.001), and age at baseline was a moderate predictor (OR 1.031, 95%CI 1.003–1.060; p = 0.029). Conclusions: The PET/CT scan is, preferably in combination with parasite-specific serology and IgE levels, a valuable tool in the clinical management of AE and is able to predict the course of the disease.

Background Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and in viral infections of the central nervous system is increasing and specific inhibitors are available as therapeutic options. Methods In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to noninflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using postmortem brain tissue samples. Results We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent, and C3 complement deposits were detected in postmortem brain sections. Intrathecal complement levels were negatively correlated with survival. Conclusions Further investigations are warranted to clarify whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis. [ABSTRACT FROM AUTHOR]

Postencephalitic parkinsonism (PEP) is suggested to show a virus-induced pathology, which is different from classical idiopathic Parkinson's disease (PD) as there is no α-synuclein/Lewy body pathology. However, PEP shows a typical clinical representation of motor disturbances. In addition, compared to PD, there is no iron-induced pathology. The aim of this preliminary study was to compare PEP with PD regarding iron-induced pathology, using histochemistry methods on paraffin-embedded post-mortem brain tissue. In the PEP group, iron was not seen, except for one case with sparse perivascular depositions. Rather, PEP offers a pathology related to tau-protein/neurofibrillary tangles, with mild to moderate memory deficits only. It is assumed that this virus-induced pathology is due to immunological dysfunctions causing (neuro)inflammation-induced neuronal network disturbances as events that trigger clinical parkinsonism. The absence of iron deposits implies that PEP cannot be treated with iron chelators. The therapy with L-Dopa is also not an option, as L-Dopa only leads to an initial slight improvement in symptoms in isolated cases. [ABSTRACT FROM AUTHOR]

India-Asia continental collision–induced volcanic gas emissions are thought to have played an important role in driving Cenozoic atmospheric CO2 variations, yet the details of how the deep carbon cycle may influence volcanic CO2 degassing are not understood. We present a novel study employing Mg-Zn-Mo isotopic compositions of Cenozoic ultrapotassic lavas from NW Tibet. The negative Mg-Zn isotope correlation (δ26Mg = −0.39‰ to −0.19‰; δ66Zn = +0.27‰ to +0.36‰), bolstered by petrographic analysis of mantle-derived xenoliths from these lavas, demonstrates that the ultrapotassic magmas originated from a lithospheric mantle source that had been enriched by recycled carbonate-bearing sediments rich in calcite and dolomite. Very low δ98Mo values (−0.78‰ to 0‰) relative to the average continental crust (δ98Mo = +0.10‰ to +0.35‰) further indicate that the sedimentary components were derived from the subducted Indian continental crust after its dehydration. Monte Carlo modeling estimates that the input flux of carbon (elemental C) from such sediments into the lithospheric mantle is ∼5.6 Mt/yr, with a predicted CO2 emission rate of ∼15.5 Mt/yr. We suggest that the still ongoing subduction of the Indian tectonic plate has played a crucial role in introducing substantial quantities of carbonate-rich sediments into the Tibetan lithospheric mantle, leading to the sequestration of large amounts of CO2 via carbonatite metasomatism. Hence, partial melting of such a carbon-rich mantle reservoir in an orogenic setting provides the positive feedback mechanism that can explain the high flux of volcanic CO2 during IndiaAsia collision. These findings not only highlight the importance of continental subduction, sediment recycling, and mantle metasomatism by carbon-rich melts/fluids in the generation of Tibetan ultrapotassic volcanism, but they also show how the deep carbon cycle influences volcanic CO2 degassing. [ABSTRACT FROM AUTHOR]