Wind and small mammals are complementary fungal dispersers.

Following a disturbance, dispersal shapes community composition as well as ecosystem structure and function. For fungi, dispersal is often wind or mammal facilitated, but it is unclear whether these pathways are complementary or redundant in the taxa they disperse and the ecosystem functions they provide. Here, we compare the diversity and morphology of fungi dispersed by wind and three rodent species in recently harvested forests using a combination of microscopy and Illumina sequencing. We demonstrate that fungal communities dispersed by wind and small mammals differ in richness and composition. Most wind-dispersed fungi are wood saprotrophs, litter saprotrophs, and plant pathogens, whereas fungi dispersed in mammal scat are primarily mycorrhizal, soil saprotrophs, and unspecified saprotrophs. We note substantial dispersal of truffles and agaricoid mushrooms by small mammals, and dispersal of agaricoid mushrooms, crusts, and polypores by wind. In addition, we find mammal-dispersed spores are larger than wind-dispersed spores. Our findings suggest that wind- and small-mammal-facilitated dispersal are complementary processes and highlight the role of small mammals in dispersing mycorrhizal fungi, particularly following disturbances such as timber harvest.

A Geographic Information System Approach to Map Tick Exposure Risk at a Scale for Public Health Intervention.

Tick-borne disease control and prevention have been largely ineffective compared to the control of other vector-borne diseases. Although control strategies exist, they are costly or ineffective at large spatial scales. We need tools to target these strategies to places of highest tick exposure risk. Here we present a geographic information system (GIS) method for mapping predicted tick exposure risk at a 200 m by 200 m resolution, appropriate for public health intervention. We followed the approach used to map tick habitat suitability over large areas. We used drag-cloth sampling to measure the density of nymphal blacklegged ticks (Ixodes scapularis, Say (Acari: Ixodidae)) at 24 sites in Addison and Rutland Counties, VT, United States. We used a GIS to average habitat, climatological, land-use/land-cover, and abiotic characteristics over 100 m, 400 m, 1,000 m, and 2,000 m buffers around each site to evaluate which characteristic at which buffer size best predicted density of nymphal ticks (DON). The relationships between predictor variables and DON were determined with random forest models. The 100 m buffer model performed best and explained 37.7% of the variation in DON, although was highly accurate at classifying sites as having below or above average DON. This model was applied to Addison County, VT, to predict tick exposure risk at a 200 m resolution. This GIS approach to map predicted DON over a small area with fine resolution, could be used to target public health campaigns and land management practices to reduce human exposure to ticks.

Gas-Particle Partitioning and SOA Yields of Organonitrate Products from NO3-Initiated Oxidation of Isoprene under Varied Chemical Regimes.

Alkyl nitrate (AN) and secondary organic aerosol (SOA) from the reaction of nitrate radicals (NO3) with isoprene were observed in the Simulation of Atmospheric PHotochemistry In a large Reaction (SAPHIR) chamber during the NO3Isop campaign in August 2018. Based on 15 day-long experiments under various reaction conditions, we conclude that the reaction has a nominally unity molar AN yield (observed range 90 ± 40%) and an SOA mass yield of OA + organic nitrate aerosol of 13-15% (with ∼50 µg m-3 inorganic seed aerosol and 2-5 µg m-3 total organic aerosol). Isoprene (5-25 ppb) and oxidant (typically ∼100 ppb O3 and 5-25 ppb NO2) concentrations and aerosol composition (inorganic and organic coating) were varied while remaining close to ambient conditions, producing similar AN and SOA yields under all regimes. We observe the formation of dinitrates upon oxidation of the second double bond only once the isoprene precursor is fully consumed. We determine the bulk partitioning coefficient for ANs (K p ∼ 10-3 m3 µg-1), indicating an average volatility corresponding to a C5 hydroxy hydroperoxy nitrate.

Probability assessment of intracerebral hemorrhage in prehospital emergency patients.

BACKGROUND: Routing of patients with intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) to the most appropriate hospital is challenging for emergency medical services particularly when specific treatment options are only provided by specialized hospitals and determination of the exact diagnosis is difficult. We aimed to develop a prehospital score - called prehospital-intracerebral hemorrhage score (ph-ICH score) - to assist in discriminating between both conditions. METHODS: The ph-ICH score was developed with data from patients treated aboard a mobile stroke unit in Berlin, Germany, between 2011 and 2013 (derivation cohort) and in 2018 (validation cohort). Diagnosis of ICH or AIS was established using clinical data and neuroradiological cerebral imaging. Diagnostic accuracy was measured with significance testing, Cohen's d and receiver-operating-characteristics. RESULTS: We analyzed 416 patients (32 ICH, 224 AIS, 41 transient ischemic attack, 119 stroke mimic) in the derivation cohort and 285 patients (33 ICH and 252 AIS) in the validation cohort. Systolic blood pressure, level of consciousness and severity of neurological deficits (i. e. certain items of the National Institutes of Health Stroke Scale) were used to calculate the ph-ICH score that showed higher values in the ICH compared to the AIS group (derivation cohort: 1.8 ± 1.2 vs. 1.0 ± 0.9 points; validation cohort: 1.8 ± 0.9 vs. 0.8 ± 0.7 points; d = 0.9 and 1.4, both p < 0.01). Receiver-operating-characteristics showed fair and good accuracy with an area under the curve of 0.71 for the derivation and 0.81 for the validation cohort. CONCLUSIONS: The ph-ICH score can assist medical personnel in the field to assess the likelihood of ICH and AIS in emergency patients.

An improved method for high-throughput quantification of autophagy in mammalian cells.

Autophagy is a cellular homeostatic pathway with functions ranging from cytoplasmic protein turnover to immune defense. Therapeutic modulation of autophagy has been demonstrated to positively impact the outcome of autophagy-dysregulated diseases such as cancer or microbial infections. However, currently available agents lack specificity, and new candidates for drug development or potential cellular targets need to be identified. Here, we present an improved method to robustly detect changes in autophagy in a high-throughput manner on a single cell level, allowing effective screening. This method quantifies eGFP-LC3B positive vesicles to accurately monitor autophagy. We have significantly streamlined the protocol and optimized it for rapid quantification of large numbers of cells in little time, while retaining accuracy and sensitivity. Z scores up to 0.91 without a loss of sensitivity demonstrate the robustness and aptness of this approach. Three exemplary applications outline the value of our protocols and cell lines: (I) Examining autophagy modulating compounds on four different cell types. (II) Monitoring of autophagy upon infection with e.g. measles or influenza A virus. (III) CRISPR/Cas9 screening for autophagy modulating factors in T cells. In summary, we offer ready-to-use protocols to generate sensitive autophagy reporter cells and quantify autophagy in high-throughput assays.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

The Density of the Lyme Disease Vector, Ixodes scapularis (Blacklegged Tick), Differs Between the Champlain Valley and Green Mountains, Vermont.

Lyme disease is an emerging infectious disease of public health concern in the northeastern United States. The disease's vector, Ixodes scapularis (Say) (Blacklegged Tick), has increased its range in the past twenty years. In its newly endemic northern range there have been few studies of the Blacklegged Tick's habitat associations. From 2016-2018, we sampled for nymphal Blacklegged Ticks in the Champlain Valley and Green Mountains of Addison County, Vermont, and tested them for Borrelia burgdorferi, the Lyme disease agent. We found 10 times more ticks in the Champlain Valley than in the Green Mountains. Nymphal infection prevalence was 0.21 and did not vary by year or region. The difference in tick density reported has public health consequences, as Vermont has one of the highest rates of Lyme disease in the United States.

Telemedicine in Prehospital Acute Stroke Care.

Background Mobile stroke units ( MSU s), equipped with an integrated computed tomography scanner, can shorten time to thrombolytic treatment and may improve outcome in patients with acute ischemic stroke. Original (German) MSU s are staffed by neurologists trained as emergency physicians, but patient assessment and treatment decisions by a remote neurologist may offer an alternative to neurologists aboard MSU . Methods and Results Remote neurologists examined and assessed emergency patients treated aboard the MSU in Berlin, Germany. Audiovisual quality was rated by the remote neurologist from 1 (excellent) to 6 (insufficient), and duration of video examinations was assessed. We analyzed interrater reliability of diagnoses, scores on the National Institutes of Health Stroke Scale and treatment decisions (intravenous thrombolysis) between the MSU neurologist and the remote neurologist. We included 90 of 103 emergency assessments (13 patients were excluded because of either failed connection, technical problems, clinical worsening during teleconsultation, or missing data in documentation) in this study. The remote neurologist rated audiovisual quality with a median grade for audio quality of 3 (satisfactory) and for video quality of 2 (good). Mean time for completion of teleconsultations was about 19±5 minutes. The interrater reliabilities between the onboard and remote neurologist were high for diagnoses (Cohen's κ=0.86), National Institutes of Health Stroke Scale sum scores (intraclass correlation coefficient, 0.87) and treatment decisions (16 treatment decisions agreed versus 2 disagreed; Cohen's κ=0.93). Conclusions Remote assessment and treatment decisions of emergency patients are technically feasible with satisfactory audiovisual quality. Agreement on diagnoses, neurological examinations, and treatment decisions between onboard and remote neurologists was high.

A Probabilistic Framework for Risk Analysis of Widespread Flood Events: A Proof-of-Concept Study.

This article presents a flood risk analysis model that considers the spatially heterogeneous nature of flood events. The basic concept of this approach is to generate a large sample of flood events that can be regarded as temporal extrapolation of flood events. These are combined with cumulative flood impact indicators, such as building damages, to finally derive time series of damages for risk estimation. Therefore, a multivariate modeling procedure that is able to take into account the spatial characteristics of flooding, the regionalization method top-kriging, and three different impact indicators are combined in a model chain. Eventually, the expected annual flood impact (e.g., expected annual damages) and the flood impact associated with a low probability of occurrence are determined for a study area. The risk model has the potential to augment the understanding of flood risk in a region and thereby contribute to enhanced risk management of, for example, risk analysts and policymakers or insurance companies. The modeling framework was successfully applied in a proof-of-concept exercise in Vorarlberg (Austria). The results of the case study show that risk analysis has to be based on spatially heterogeneous flood events in order to estimate flood risk adequately.

Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients.

BACKGROUND: Patients with a sudden onset of focal neurological deficits consistent with stroke, who turn out to have alternative conditions, have been labeled stroke mimics. AIMS: We assessed a recently validated telemedicine-based stroke mimic score (TeleStroke mimic score; TM-score) and individual patient characteristics with regard to its discriminative value between cerebrovascular disease and stroke mimic patients in the in-person, pre-hospital setting. METHODS: We evaluated patients cared for in a mobile stroke unit in Berlin, Germany. We investigated whether the TM-score (comprising six parameters), Face Arm Speech Time test, and individual patient characteristics were able to differentiate cerebrovascular disease from stroke mimic patients. RESULTS: We included 423 patients (299 (70.7%) cerebrovascular disease and 124 (29.3%) stroke mimic) in the final analysis. A TM-score > 30 indicated a high probability of a cerebrovascular disease and a score ≤15 of a stroke mimic. The TM-score performed well to identify stroke mimics (area under the curve of 0.74 under receiver-operating characteristic curve analysis). The cerebrovascular disease patients were older (74.8 vs. 69.8 years, p = 0.001), had more often severe strokes (NIHSS > 14 25.8% vs. 11.3%, p = 0.001), presented more often with weakness of the face (70.9% vs. 42.7%, p = 0.001) or arm (60.9% vs. 33.9%, p = 0.001), dysarthria (59.5% vs. 40.3%, p < 0.001), history of atrial fibrillation (38.1% vs. 21.0%, p = 0.001), arterial hypertension (78.9% vs. 53.2%, p < 0.001), and less often with seizure (0.7% vs. 21.0%, p < 0.001). CONCLUSIONS: The TM-score and certain patient characteristics can help paramedics and emergency physicians in the field to identify stroke mimic patients and select the most appropriate hospital destination.

Association of Gnrhr mRNA With the Stem Cell Determinant Musashi: A Mechanism for Leptin-Mediated Modulation of GnRHR Expression.

The cyclic expression of pituitary gonadotropin-releasing hormone receptors (GnRHRs) may be an important checkpoint for leptin regulatory signals. Gonadotrope Lepr-null mice have reduced GnRHR levels, suggesting these receptors may be leptin targets. To determine if leptin stimulated GnRHR directly, primary pituitary cultures or pieces were exposed to 1 to 100 nM leptin. Leptin increased GnRHR protein levels and the percentages of gonadotropes that bound biotinylated analogs of gonadotropin-releasing hormone (bio-GnRH) but had no effect on Gnrhr messenger RNA (mRNA). An in silico analysis revealed three consensus Musashi (MSI) binding elements (MBEs) for this translational control protein in the 3' untranslated region (UTR) of Gnrhr mRNA. Several experiments determined that these Gnrhr mRNA MBE were active: (1) RNA electrophoretic mobility shift assay analyses showed that MSI1 specifically bound Gnrhr mRNA 3'-UTR; (2) RNA immunoprecipitation of pituitary fractions with MSI1 antibody pulled down a complex enriched in endogenous MSI protein and endogenous Gnrhr mRNA; and (3) fluorescence reporter assays showed that MSI1 repressed translation of the reporter coupled to the Gnrhr 3'-UTR. In vitro, leptin stimulation of pituitary pieces reduced Msi1 mRNA in female pituitaries, and leptin stimulation of pituitary cultures reduced MSI1 proteins selectively in gonadotropes identified by binding to bio-GnRH. These findings show that leptin's direct stimulatory actions on gonadotrope GnRHR correlate with a direct inhibition of expression of the posttranscriptional regulator MSI1. We also show MSI1 interaction with the 3'-UTR of Gnrhr mRNA. These findings now open the door to future studies of leptin-modulated posttranscriptional pathways.

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage.

BACKGROUND: Both, acute ischemic stroke (AIS) and hemorrhage stroke (intracerebral hemorrhage, ICH) require early attention but different treatment strategies. Plasma glial fibrillary acidic protein (GFAP) levels were found to be elevated in ICH patients after they arrived in the hospital. Because treatment options differed, we sought to determine whether GFAP can be used to accurately differentiate between of AIS and ICH in the prehospital setting. METHODS: We assessed acute stroke patients in the Stroke Emergency Mobile (STEMO). STEMO is a stroke ambulance staffed by a specialized team including a neurologist and equipped with a computed tomography scanner plus a point-of-care laboratory. The STEMO ambulance is integrated in the emergency medical system of Berlin, Germany. Following prehospital stroke diagnosis, blood was drawn and subsequently analysed using research assays from Roche diagnostics. The clinical accuracy of plasma GFAP was tested using a cut-off value of 0.29 ng/ml. RESULTS: Blood samples of 74 patients were analysed. Twenty-five patients had ICH (mean age 69 ± 11 years, median National Institutes of Health Stroke Scale (NIHSS) 15) and 49 IS (mean age 75 ± 10 years, median NIHSS 6). Nine ICH (0 IS patients) had GFAP-levels above 0.29 ng/ml. The sensitivity and specificity of GFAP for differentiating between ICH and AIS were 36.0 and 100%. The sensitivity for ICH volume >15 ml was 61.5%. ICH patients without GFAP elevation had significantly smaller hemorrhage volumes (median 4.5 vs. 37.6 ml, p = 0.004) and were less likely to deteriorate (19 vs. 56%, p = 0.087). CONCLUSIONS: GFAP levels >0.29 ng/ml were seen only in ICH, thus confirming the diagnosis of ICH during prehospital care. However, sensitivity is low particularly in smaller hemorrhages.

Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study.

BACKGROUND: Specialised CT-equipped mobile stroke treatment units shorten time to intravenous thrombolysis in acute ischaemic stroke by starting treatment before hospital admission; however, direct effects of pre-hospital thrombolysis on clinical outcomes have not been shown. We aimed to compare 3-month functional outcomes after intravenous thrombolysis in patients with acute ischaemic who had received emergency mobile care or and conventional care. METHODS: In this observational registry study, patients with ischaemic stroke received intravenous thrombolysis (alteplase) either within a stroke emergency mobile (STEMO) vehicle (pre-hospital care covering 1·3 million inhabitants of Berlin) or within conventional care (normal ambulances and in-hospital care at the Charité Campus Benjamin Franklin in Berlin). Patient data on treatment, outcome, and demographics were documented in STEMO (pre-hospital) or conventional care (in-hospital) registries. The primary outcome was the proportion of patients who had lived at home without assistance before stroke and had a 3-month modified Rankin Scale (mRS) score of 1 or lower. Our multivariable logistic regression was adjusted for demographics, comorbidities, and stroke severity. This study is registered with ClinicalTrials.gov, number NCT02358772. FINDINGS: Between Feb 5, 2011, and March 5, 2015, 427 patients were treated within the STEMO vehicle and their data were entered into a pre-hospital registry. 505 patients received conventional care and their data were entered into an in-hospital thrombolysis registry. Of these, 305 patients in the STEMO group and 353 in the conventional care group met inclusion criteria and were included in the analysis. 161 (53%) patients in the STEMO group versus 166 (47%) in the conventional care group had an mRS score of 1 or lower (p=0·14). Compared with conventional care, adjusted odds ratios (ORs) for STEMO care for the primary outcome (OR 1·40, 95% CI 1·00-1·97; p=0·052) were not significant. Intracranial haemorrhage (p=0·27) and 7-day mortality (p=0·23) did not differ significantly between treatment groups. INTERPRETATION: We found no significant difference between the proportion of patients with a mRS score of 1 or lower receiving STEMO care compared with conventional care. However, our results suggest that pre-hospital start of intravenous thrombolysis might lead to improved functional outcome in patients. This evidence requires substantiation in future large-scale trials. FUNDING: Zukunftsfonds Berlin, the Technology Foundation Berlin with EU co-financing by the European Regional Development Fund via Investitionsbank Berlin, and the German Federal Ministry for Education and Research via the Center for Stroke Research Berlin.

Influence of Distance to Scene on Time to Thrombolysis in a Specialized Stroke Ambulance.

BACKGROUND AND PURPOSE: Specialized computed tomography-equipped stroke ambulances shorten time to intravenous thrombolysis in acute ischemic stroke by starting treatment before hospital arrival. Because of longer travel-time-to-scene, time benefits of this concept are expected to diminish with longer distances from base station to scene. METHODS: We used data from the Prehospital Acute Neurological Treatment and Optimization of Medical Cares in Stroke (PHANTOM-S) trial comparing time intervals between patients for whom a specialized stroke ambulance (stroke emergency mobile) was deployed and patients with conventional emergency medical service. Expected times from base station to scene had been calculated beforehand using computer algorithms informed by emergency medical service routine data. Four different deployment zones with-75% probability-expected arrival within 4, 8, 12, and 16 minutes and total population coverage of ≈1.3 million inhabitants were categorized for stroke emergency mobile deployment. We analyzed times from alarm-to-arrival at scene, to start of intravenous thrombolysis and from onset-to-intravenous thrombolysis. RESULTS: Corresponding to the size of the respective catchment zone, the number of patients cared increased with distance (zone 1: n=30, zone 2: n=127, zone 3: n=156, and zone 4: n=217). Although time to stroke emergency mobile arrival increased with distance (mean: 8.0, 12.5, 15.4, and 18.4 minutes in zones 1-4), time from alarm-to-intravenous thrombolysis (mean: 41.8 versus 76.5; 50.2 versus 79.1; 54.5 versus 76.6; and 59.3 versus 78.0 minutes, respectively; all P<0.01) remained shorter in the stroke emergency mobile group across all zones. CONCLUSIONS: In a metropolitan area such as Berlin, time benefits justify a specialized stroke ambulance service up to a mean travel time of 18 minutes from base station. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01382862.

Overcoming the Interface Losses in Planar Heterojunction Perovskite-Based Solar Cells.

A scalable, hysteresis-free and planar architecture perovskite solar cell is presented, employing a flame spray synthesized low-temperature processed NiO (LT-NiO) as hole-transporting layer yielding efficiencies close to 18%. Importantly, it is found that LT-NiO boosts the limits of open-circuit voltages toward an impressive non-radiative voltage loss of 0.226 V only, whereas PEDOT: PSS suffers from significant large non-radiative recombination losses.

Compressed sensing electron tomography of needle-shaped biological specimens--Potential for improved reconstruction fidelity with reduced dose.

Electron tomography is an invaluable method for 3D cellular imaging. The technique is, however, limited by the specimen geometry, with a loss of resolution due to a restricted tilt range, an increase in specimen thickness with tilt, and a resultant need for subjective and time-consuming manual segmentation. Here we show that 3D reconstructions of needle-shaped biological samples exhibit isotropic resolution, facilitating improved automated segmentation and feature detection. By using scanning transmission electron tomography, with small probe convergence angles, high spatial resolution is maintained over large depths of field and across the tilt range. Moreover, the application of compressed sensing methods to the needle data demonstrates how high fidelity reconstructions may be achieved with far fewer images (and thus greatly reduced dose) than needed by conventional methods. These findings open the door to high fidelity electron tomography over critically relevant length-scales, filling an important gap between existing 3D cellular imaging techniques.

Coexistence of both gyroid chiralities in individual butterfly wing scales of Callophrys rubi.

The wing scales of the Green Hairstreak butterfly Callophrys rubi consist of crystalline domains with sizes of a few micrometers, which exhibit a congenitally handed porous chitin microstructure identified as the chiral triply periodic single-gyroid structure. Here, the chirality and crystallographic texture of these domains are investigated by means of electron tomography. The tomograms unambiguously reveal the coexistence of the two enantiomeric forms of opposite handedness: the left- and right-handed gyroids. These two enantiomers appear with nonequal probabilities, implying that molecularly chiral constituents of the biological formation process presumably invoke a chiral symmetry break, resulting in a preferred enantiomeric form of the gyroid structure. Assuming validity of the formation model proposed by Ghiradella H (1989) J Morphol 202(1):69-88 and Saranathan V, et al. (2010) Proc Natl Acad Sci USA 107(26):11676-11681, where the two enantiomeric labyrinthine domains of the gyroid are connected to the extracellular and intra-SER spaces, our findings imply that the structural chirality of the single gyroid is, however, not caused by the molecular chirality of chitin. Furthermore, the wing scales are found to be highly textured, with a substantial fraction of domains exhibiting the <001> directions of the gyroid crystal aligned parallel to the scale surface normal. Both findings are needed to completely understand the photonic purpose of the single gyroid in gyroid-forming butterflies. More importantly, they show the level of control that morphogenesis exerts over secondary features of biological nanostructures, such as chirality or crystallographic texture, providing inspiration for biomimetic replication strategies for synthetic self-assembly mechanisms.

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration.

OBJECTIVES: To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. SUBJECTS AND METHODS: A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. RESULTS: Case patients were reflective of interstitial cystitis epidemiology with age range from 26-88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89-24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17-17.4). CONCLUSION: The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation.

Striatal Infarction Elicits Secondary Extrafocal MRI Changes in Ipsilateral Substantia Nigra.

Focal ischemia may induce pathological alterations in brain areas distant from the primary lesion. In animal models, exofocal neuron death in the ipsilateral midbrain has been described after occlusion of the middle cerebral artery (MCA). Using sequential magnetic resonance imaging (T2- and diffusion-weighted) at 3 Tesla, we investigated acute ischemic stroke patients on days 1, 2, 6, 8, and 10 after stroke onset. Sixteen consecutive patients who had suffered a stroke involving the caudate nucleus and/or putamen of either hemisphere were recruited into the study. Four additional patients with strokes sparing the caudate nucleus and putamen but encompassing at least one-third of the MCA territory served as controls. Ischemic lesions involving striatal structures resulted in hyperintense lesions in ipsilateral midbrain that emerged between days 6 and 10 after stroke and were not present on the initial scans. In contrast, none of the control stroke patients developed secondary midbrain lesions. Hyperintense lesions in the pyramidal tract or the brain stem caused by degeneration of the corticospinal tract could be clearly distinguished from these secondary midbrain gray matter lesions and were detectable from day 2 after ischemia. Co-registration of high-resolution images with a digitized anatomic atlas revealed localization of secondary lesions primarily in the substantia nigra pars compacta. Apparent diffusion coefficient (ADC) values in the secondary lesions showed a delayed sharp decline through day 10. Normalization of ADC values was observed at late measurements. Taken together, our study demonstrates that striatal infarction elicits delayed degenerative changes in ipsilateral substantia nigra pars compacta.