A revised genus-level classification for Cerrenaceae (Polyporales, Agaricomycetes).

Cerrenaceae is a small family of polypores and hydnoid fungi in the order Polyporales (Basidiomycota). The family consists of white-rot fungi, some of which are serious tree pathogens. Combining morphological evidence with a phylogenetic dataset of six genetic markers, we revise generic concepts in the family and propose a seven-genus classification system for the family. Two genera are introduced as new: the monotypic Acanthodontia for Radulodon cirrhatinus, and Lividopora for the Rigidoporus vinctus complex. We re-introduce the name Somion for the Spongipellis delectans complex. Other recognized genera in the family are Cerrena, Irpiciporus, Pseudolagarobasidium, and Radulodon. New species introduced are Irpiciporus branchiformis from Tanzania, Lividopora armeniaca, and L. facilis from Southeast Asia, and Somion strenuum from East Asia. We provide nomenclatural comments on all the names combined to the above Cerrenaceae genera and typify Cerrena unicolor, C. zonata, Polyporus carneopallens (= L. vincta), Somion occarium, and S. unicolor. The genus Hyphoradulum belongs to Cystostereaceae (Agaricales), and we transfer the type species H. conspicuum to Crustomyces. Our study highlights the importance of integrating different basidiocarp types in analyses when revising genus classification in macrofungi. Citation: Miettinen O, Vlasák J, Larsson E, Vlasák J Jr., Seelan JSS, Hernawati, Levicky Q, Larsson K-H, Spirin V (2023). A revised genus-level classification for Cerrenaceae (Polyporales, Agaricomycetes). Fungal Systematics and Evolution 12: 271-322. doi: 10.3114/fuse.2023.12.14.

Fungal Planet description sheets: 1436-1477.

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilaxglyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.

Hygrophorus sect. Olivaceoumbrini: new boundaries, extended biogeography and unexpected diversity unravelled by transatlantic studies.

As currently delineated, Hygrophorus sect. Olivaceoumbrini is a polyphyletic assembly within subg. Colorati, encompassing glutinous and pigmented taxa. According to available literature, between a dozen and twenty species may belong in the section, mostly represented in continental and boreal forests of Europe and North America. However, the limited phylogenetic and biogeographic coverage of the genus does not presently allow for a reliable assessment of its taxonomic boundaries, nor does it provide a complete picture of species diversity within sect. Olivaceoumbrini. In an ongoing effort to confer an evolutionary backbone to Hygrophorus systematics, we assembled and analysed a dataset comprising 268 intercontinental sequences, including holotypes of 7 taxa previously not positioned phylogenetically, and enriched with collections from largely unexplored Mediterranean and Anatolian ecosystems. Overall, 30 clades are identified within 5 distinct lineages, including 11 species putatively new to science. Seven of these are formally described here as H. agathosmoides, H. albofloccosus, H. canadensis, H. limosus, H. marcocontui, H. pinophilus and H. pustulatoides spp. nov. This enriched coverage of section Olivaceoumbrini s.lat. calls for a re-evaluation of its natural boundaries into a core monophyletic clade, including H. olivaceoalbus and five closely related lookalikes, as well as the assignment of the section rank to the four remaining lineages: sect. Fuscocinerei sect. nov., sect. Limacini sect. nov., sect. Nudolidi sect. nov. and sect. Tephroleuci, respectively. We also stabilize the usage of six historical names, H. glutinifer, H. hyacinthinus, H. mesotephrus, H. olivaceoalbus, H. pustulatus and H. tephroleucus, through designation of two neotypes, three lectotypes and four epitypes. Citation: Bellanger J-M, Lebeuf R, Sesli E, et al. 2021. Hygrophorus sect. Olivaceoumbrini: new boundaries, extended biogeography and unexpected diversity unravelled by transatlantic studies. Persoonia 46: 272-312. https://doi.org/10.3767/persoonia.2021.46.10.

Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema.

Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease.

BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling-derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease. MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient's 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute-based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively. RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968-0.988) and 1.8 percentage points (95% CI, 0.3-3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively. CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

Risk factors and outcomes of chronic opioid use following trauma.

BACKGROUND: The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality. METHODS: Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored. RESULTS: Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6-18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure. CONCLUSION: Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6-18 months after trauma.

ANTECEDENTES: El uso indebido de opioides es un problema creciente que se ha convertido en una grave crisis en muchos países. No se ha analizado el papel de las lesiones traumáticas como puerta de entrada al uso de opioides. Se estableció la hipótesis de que una lesión traumática podría asociarse con el uso crónico de opioides y acompañarse de un aumento de la mortalidad a largo plazo. MÉTODOS: Se ajustaron por edad, sexo y municipio a los pacientes suecos con lesiones traumáticas y sus controles. Después de vincular varios registros de salud suecos, se evaluó el consumo de opioides antes y después de la lesión traumática. En los pacientes con lesiones traumáticas, se utilizó una regresión logística para definir los factores asociados con el uso crónico de opioides, definida como una receta prescrita y dispensada en el segundo trimestre después de la lesión traumática, y ​​una regresión de Cox para estudiar el exceso de riesgo de mortalidad. Además, se exploraron las causas de muerte de los usuarios de opioides postraumáticos. RESULTADOS: Se analizaron 13.309 pacientes con lesiones traumáticas y 70.621 controles. La exposición a una lesión traumática se asoció de forma independiente con el uso crónico de opioides, (razón de oportunidades, odds ratio, OR) OR 3,3 (i.c. del 95% 3,0-3,6), y dicho uso se asoció con la edad, el bajo nivel educativo, las comorbilidad físicas y psiquiátricas, el uso previo de opioides y la gravedad de las lesiones. El cociente de riesgos instantáneos, hazard ratio, HR ajustado de muerte por cualquier causa a los 6-18 meses de la lesión traumática para los consumidores crónicos de opioides fue de 1,8 (i.c. del 95% 1,3-2,5). En un subconjunto de pacientes con lesiones traumáticas sin exposición previa a los opioides, los hallazgos fueron similares. CONCLUSIÓN: La lesión traumática se asoció con el uso crónico de opioides. Estos pacientes presentan un exceso de riesgo de mortalidad entre los 6 y 8 meses después del trauma.

Fungal Planet description sheets: 1112-1181.

Novel species of fungi described in this study include those from various countries as follows: Australia, Austroboletus asper on soil, Cylindromonium alloxyli on leaves of Alloxylon pinnatum, Davidhawksworthia quintiniae on leaves of Quintinia sieberi, Exophiala prostantherae on leaves of Prostanthera sp., Lactifluus lactiglaucus on soil, Linteromyces quintiniae (incl. Linteromyces gen. nov.) on leaves of Quintinia sieberi, Lophotrichus medusoides from stem tissue of Citrus garrawayi, Mycena pulchra on soil, Neocalonectria tristaniopsidis (incl. Neocalonectria gen. nov.) and Xyladictyochaeta tristaniopsidis on leaves of Tristaniopsis collina, Parasarocladium tasmanniae on leaves of Tasmannia insipida, Phytophthora aquae-cooljarloo from pond water, Serendipita whamiae as endophyte from roots of Eriochilus cucullatus, Veloboletus limbatus (incl. Veloboletus gen. nov.) on soil. Austria, Cortinarius glaucoelotus on soil. Bulgaria, Suhomyces rilaensis from the gut of Bolitophagus interruptus found on a Polyporus sp. Canada, Cantharellus betularum among leaf litter of Betula, Penicillium saanichii from house dust. Chile, Circinella lampensis on soil, Exophiala embothrii from rhizosphere of Embothrium coccineum. China, Colletotrichum cycadis on leaves of Cycas revoluta. Croatia, Phialocephala melitaea on fallen branch of Pinus halepensis. Czech Republic, Geoglossum jirinae on soil, Pyrenochaetopsis rajhradensis from dead wood of Buxus sempervirens. Dominican Republic, Amanita domingensis on litter of deciduous wood, Melanoleuca dominicana on forest litter. France, Crinipellis nigrolamellata (Martinique) on leaves of Pisonia fragrans, Talaromyces pulveris from bore dust of Xestobium rufovillosum infesting floorboards. French Guiana, Hypoxylon hepaticolor on dead corticated branch. Great Britain, Inocybe ionolepis on soil. India, Cortinarius indopurpurascens among leaf litter of Quercus leucotrichophora. Iran, Pseudopyricularia javanii on infected leaves of Cyperus sp., Xenomonodictys iranica (incl. Xenomonodictys gen. nov.) on wood of Fagus orientalis. Italy, Penicillium vallebormidaense from compost. Namibia, Alternaria mirabibensis on plant litter, Curvularia moringae and Moringomyces phantasmae (incl. Moringomyces gen. nov.) on leaves and flowers of Moringa ovalifolia, Gobabebomyces vachelliae (incl. Gobabebomyces gen. nov.) on leaves of Vachellia erioloba, Preussia procaviae on dung of Procavia capensis. Pakistan, Russula shawarensis from soil on forest floor. Russia, Cyberlindnera dauci from Daucus carota. South Africa, Acremonium behniae on leaves of Behnia reticulata, Dothiora aloidendri and Hantamomyces aloidendri (incl. Hantamomyces gen. nov.) on leaves of Aloidendron dichotomum, Endoconidioma euphorbiae on leaves of Euphorbia mauritanica, Eucasphaeria proteae on leaves of Protea neriifolia, Exophiala mali from inner fruit tissue of Malus sp., Graminopassalora geissorhizae on leaves of Geissorhiza splendidissima, Neocamarosporium leipoldtiae on leaves of Leipoldtia schultzii, Neocladosporium osteospermi on leaf spots of Osteospermum moniliferum, Neometulocladosporiella seifertii on leaves of Combretum caffrum, Paramyrothecium pituitipietianum on stems of Grielum humifusum, Phytopythium paucipapillatum from roots of Vitis sp., Stemphylium carpobroti and Verrucocladosporium carpobroti on leaves of Carpobrotus quadrifolius, Suttonomyces cephalophylli on leaves of Cephalophyllum pilansii. Sweden, Coprinopsis rubra on cow dung, Elaphomyces nemoreus from deciduous woodlands. Spain, Polyscytalum pini-canariensis on needles of Pinus canariensis, Pseudosubramaniomyces septatus from stream sediment, Tuber lusitanicum on soil under Quercus suber. Thailand, Tolypocladium flavonigrum on Elaphomyces sp. USA, Chaetothyrina spondiadis on fruits of Spondias mombin, Gymnascella minnisii from bat guano, Juncomyces patwiniorum on culms of Juncus effusus, Moelleriella puertoricoensis on scale insect, Neodothiora populina (incl. Neodothiora gen. nov.) on stem cankers of Populus tremuloides, Pseudogymnoascus palmeri from cave sediment. Vietnam, Cyphellophora vietnamensis on leaf litter, Tylopilus subotsuensis on soil in montane evergreen broadleaf forest. Morphological and culture characteristics are supported by DNA barcodes.

Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery.

BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 µL; interquartile range, 69.8-142.8 µL) compared with 62.5 µL (interquartile range, 58.3-73.8 µL; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 µL (interquartile range, 81-241 µL) to 88 µL (interquartile range, 51.8-173.3 µL; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

Synthesizing a Contrast-Enhancement Map in Patients with High-Grade Gliomas Based on a Postcontrast MR Imaging Quantification Only.

BACKGROUND AND PURPOSE: Administration of a gadolinium-based contrast agent is an important diagnostic biomarker for blood-brain barrier damage. In clinical use, detection is based on subjective comparison of native and postgadolinium-based contrast agent T1-weighted images. Quantitative MR imaging studies have suggested a relation between the longitudinal relaxation rate and proton-density in the brain parenchyma, which is disturbed by gadolinium-based contrast agents. This discrepancy can be used to synthesize a contrast-enhancement map based solely on the postgadolinium-based contrast agent acquisition. The aim of this study was to compare synthetic enhancement maps with subtraction maps of native and postgadolinium-based contrast agent images. MATERIALS AND METHODS: For 14 patients with high-grade gliomas, quantitative MR imaging was performed before and after gadolinium-based contrast agent administration. The quantification sequence was multidynamic and multiecho, with a scan time of 6 minutes. The 2 image stacks were coregistered using in-plane transformation. The longitudinal relaxation maps were subtracted and correlated with the synthetic longitudinal relaxation enhancement maps on the basis of the postgadolinium-based contrast agent images only. ROIs were drawn for tumor delineation. RESULTS: Linear regression of the subtraction and synthetic longitudinal relaxation enhancement maps showed a slope of 1.02 ± 0.19 and an intercept of 0.05 ± 0.12. The Pearson correlation coefficient was 0.861 ± 0.059, and the coefficient of variation was 0.18 ± 0.04. On average, a volume of 1.71 ± 1.28 mL of low-intensity enhancement was detected in the synthetic enhancement maps outside the borders of the drawn ROI. CONCLUSIONS: The study shows that there was a good correlation between subtraction longitudinal relaxation enhancement maps and synthetic longitudinal relaxation enhancement maps in patients with high-grade gliomas. The method may improve the sensitivity and objectivity for the detection of gadolinium-based contrast agent enhancement.

Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours.

BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. RESULTS: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22-37 mm were detectable in the 111In-SPECT images and spheres larger than 13-22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. CONCLUSIONS: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.

The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation.

BACKGROUND AND PURPOSE: Despite the important role of imaging in diagnosing idiopathic normal-pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms. METHODS: In this prospective, population-based study of iNPH, 168 individuals (93 females) [mean age 75 (range 66-92) years] underwent computed tomography of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters, i.e. Evans' index, callosal angle, size of temporal horns, narrow high-convexity sulci, dilated Sylvian fissures, focally dilated sulci, peri-ventricular hypodensities and bulging of the lateral ventricular roof. RESULTS: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total iNPH Radscale score and clinical symptoms. The inter-rater agreement for the included radiological parameters was high (intraclass correlation, 0.74-0.97). CONCLUSION: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms should raise suspicion of iNPH, motivating further evaluation for shunt surgery.

A clinical and histopathological comparison of the effectiveness of salicylic acid to a compound of inorganic acids for the treatment of digital dermatitis in cattle.

Bovine digital dermatitis (DD) is a painful infectious disease, causing lameness, reduced animal welfare, and production losses in dairy herds. The main factors contributing to DD are an infection with Treponema spp. and poor hygiene. Topical treatment has primarily consisted of antibiotics; however, the demand for effective nonantibiotic alternatives is increasing. The objective was to evaluate the performance of 3 nonantibiotic topical treatments (salicylic acid and a compound of inorganic acids in a 20% solution and in a dry form) on DD in a commercial dairy herd. Within the 30-d test period, 42 DD lesions on 33 Holstein cows were assigned to receive 1 of the 3 treatments. Lesions were biopsied before and after treatment and were clinically evaluated 5 times. Improved lesions were clinically defined as either healed (regeneration of the skin) or healing (dry lesions covered by a scab). Unhealed lesions were defined as either active [with a raw, moist, strawberry-like (granulating) surface] or mature (with a raised papillomatous appearance). The effectiveness of treatment was evaluated histopathologically using the following scores: 0 (no spirochetes present), 1 (small number of spirochetes present in the epidermis), 2 (moderate number of spirochetes present and reaching an intermediary level in the epidermis), and 3 (large number of spirochetes present and reaching the deepest part of the epidermis or the superficial dermis). The improvement rate was 10/14 (71%) for salicylic acid, 11/15 (73%) for the inorganic acid solution, and 8/13 (62%) for the inorganic acid powder. The analysis showed no difference among treatments. The association between clinical score and histopathological score was determined by an odds ratio. The odds ratio of a healed lesion having spirochetes in the epidermis was 0.58 and that of an active DD lesion having spirochetes in the epidermis was 26.5.

Arterial Spin-Labeling Perfusion MR Imaging Demonstrates Regional CBF Decrease in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF. MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses. RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001). CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.

Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study.

The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [11C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [11C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [11C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [11C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

Rapid and Accurate MRI Segmentation of Peritumoral Brain Edema in Meningiomas.

PURPOSE: The extent of peritumoral brain edema (PTBE) in meningiomas commonly affects the clinical outcome. Despite its importance, edema volume is usually highly inaccurately approximated to a spheroid shape. We tested the accuracy and the reproducibility of semiautomatic lesion management software for the analysis of PTBE in a homogeneous case series of surgically confirmed intracranial meningiomas. METHODS: PTBE volume was calculated on magnetic resonance images in 50 patients with intracranial meningiomas using commercial lesion management software (Vue PACS Livewire, Carestream, Rochester, NY, USA). Inter and intraobserver agreement evaluation and a comparison between manual volume calculation, the semiautomatic software and spheroid approximation were performed in 22 randomly selected patients. RESULTS: The calculation of edema volume was possible in all cases irrespective of the extent of the signal changes. The median time for each calculation was 3 min. Interobserver and intraobserver agreement confirmed the reproducibility of the method. Comparison with standard (fully manual) calculation confirmed the accuracy of this software. CONCLUSIONS: Our study showed a high level of reproducibility of this semiautomatic computational method for peritumoral brain edema. It is rapid and easy to use after relatively short training and is suitable for implementation in clinical practice.

X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models.

In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

Causes of excessive late death after trauma compared with a matched control cohort.

BACKGROUND: Studies on mortality following trauma have been restricted mainly to in-hospital or 30-day death. Mortality risk may be sustained several years after trauma, but the causes of late death have not been elucidated. The aim was to investigate mortality and analyse causes of late death after trauma. METHODS: All injured patients from a regional trauma registry with long-term follow-up were matched in a 1 : 5 ratio with uninjured controls by age, sex and municipality. By linkage to national registries, long-term mortality, causes of death and co-morbidity status were identified. Excess mortality was examined by calculating the all-cause mortality rate ratio (MRR). RESULTS: Among the trauma cohort of 7382 patients, 662 (9·0 per cent) died within 3 years after the index trauma; the 30-day mortality rate was 5·0 per cent. Compared with the control group (36 759 individuals), there was a sustained increase in mortality up to 3 years after trauma; the MRR was 2·88 (95 per cent c.i. 2·37 to 3·50) for days 31-365, 1·59 (1·24 to 2·04) for years 1-2 and 1·43 (1·06 to 1·92) for years 2-3. External causes, including new trauma, were far more common causes of late death in injured patients than in matched controls. CONCLUSION: Postinjury mortality is increased for several years after trauma. Excess mortality is largely attributed to recurrent trauma and other external causes of death.

Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2.

BACKGROUND: Prostate cancer ranks as the second most lethal malignancy in the Western world. Previous targeting of prostate-specific antigen and human kallikrein-related peptidase 2, two related enzymes abundantly expressed in prostatic malignancies, with radioimmunoconjugates intended for diagnostic purposes, have proven successful in rodent prostate cancer (PCa) models. In this study, we investigated the uptake and therapeutic efficacy of (177)Lu-m11B6, a human kallikrein-related peptidase 2 (hK2)-targeting radioimmunoconjugate in a pre-clinical setting. METHODS: The murine 11B6 antibody, m11B6, with high affinity for hK2, was labeled with (177)Lu. Therapy planning was done from a biokinetic study in LNCaP xenografts, and therapeutic activities of (177)Lu-m11B6 were administered to groups of mice. Body weight and general conditions of the mice were followed over a period of 120 days. RESULTS: The tumor uptake in LNCaP xenografts was 30 ± 8.2 % injected activity per gram 1 week post-injection. In vivo targeting was hK2-specific as verified by a 2.5-fold decrease in tumor uptake in pre-dosed xenografts or by a fourfold lower tumor accumulation in hK2-negative DU 145 xenografts. Therapy showed a dose-dependent efficacy in LNCaP xenografts treated with (177)Lu-m11B6. No therapeutic effect was seen in the control groups. The median survival for the lowest given activity of (177)Lu-m11B6 was 88 days compared to that of 38 days in mice given labeled non-specific IgG. For the higher administrated activities, total tumor regression was seen with minimal normal organ toxicity. CONCLUSIONS: We have proven the possibility of radioimmunotherapy targeting hK2 in subcutaneous prostate cancer xenografts. (177)Lu-m11B6 exhibited high therapeutic efficacy, with low observed toxicity. Additionally, an evaluation of the concept of pre-therapy planning using a dosimetry model was included in this radioimmunotherapy study.