Early prognosticators of later TSPO-PET-measurable microglial activation in multiple sclerosis.

BACKGROUND: Factors driving increased innate immune cell activation in multiple sclerosis (MS) brain are not well understood. As higher prevalence of microglial/macrophage activation in association with chronic lesions and diffusely in the normal appearing white matter predict more rapid accumulation of clinical disability, it is of high importance to understand processes behind this. Objective of the study was to explore demographic, clinical and paraclinical variables associating with later positron emission tomography (PET)-measurable innate immune cell activation. METHODS: PET-imaging using a TSPO-binding [11C]PK11195 was performed to evaluate microglial activation in patients with relapsing-remitting MS aged 40-55 years with a minimum disease duration of five years (n = 37). Medical records and diagnostic MR images were reviewed for relevant early MS disease-related clinical and paraclinical parameters. RESULTS: More prominent microglial activation was associated with higher number of T2 lesions in the diagnostic MRI, a higher immunoglobulin G (IgG) index in the diagnostic CSF and Expanded Disability Status Scale (EDSS) ≥ 2.0 five years after diagnosis. CONCLUSION: The number of T2 lesions in MRI, and CSF immunoglobulin content measured by IgG index at the time of MS diagnosis associated with later TSPO-PET-measurable innate immune cell activation. This suggests that both focal and diffuse early inflammatory phenomena impact the development of later progression-related pathology.

Arctic systems in the Quaternary: ecological collision, faunal mosaics and the consequences of a wobbling climate.

Climate oscillations and episodic processes interact with evolution, ecology and biogeography to determine the structure and complex mosaic that is the biosphere. Parasites and parasite-host assemblages are key components in a general explanatory paradigm for global biodiversity. We explore faunal assembly in the context of Quaternary time frames of the past 2.6 million years, a period dominated by episodic shifts in climate. Climate drivers cross a continuum from geological to contemporary timescales and serve to determine the structure and distribution of complex biotas. Cycles within cycles are apparent, with drivers that are layered, multifactorial and complex. These cycles influence the dynamics and duration of shifts in environmental structure on varying temporal and spatial scales. An understanding of the dynamics of high-latitude systems, the history of the Beringian nexus (the intermittent land connection linking Eurasia and North America) and downstream patterns of diversity depend on teasing apart the complexity of biotic assembly and persistence. Although climate oscillations have dominated the Quaternary, contemporary dynamics are driven by tipping points and shifting balances emerging from anthropogenic forces that are disrupting ecological structure. Climate change driven by anthropogenic forcing has supplanted a history of episodic variation and is eliminating ecological barriers and constraints on development and distribution for pathogen transmission. A framework to explore interactions of episodic processes on faunal structure and assembly is the Stockholm Paradigm, which appropriately shifts the focus from cospeciation to complexity and contingency in explanations of diversity.

The associations of indoor environment and psychosocial factors on the subjective evaluation of Indoor Air Quality among lower secondary school students: a multilevel analysis.

Subjective evaluation of Indoor Air Quality (subjective IAQ) reflects both building-related and psychosocial factors, but their associations have rarely been studied other than on the individual level in occupational settings and their interactions have not been assessed. Therefore, we studied whether schools' observed indoor air problems and psychosocial factors are associated with subjective IAQ and their potential interactions. The analysis was performed with a nationwide sample (N = 195 schools/26946 students) using multilevel modeling. Two datasets were merged: (i) survey data from students, including information on schools' psychosocial environment and subjective IAQ, and (ii) data from school principals, including information on observed indoor air problems. On the student level, school-related stress, poor teacher-student relationship, and whether the student did not easily receive help from school personnel, were significantly associated with poor subjective IAQ. On the school level, observed indoor air problem (standardized ß = -0.43) and poor teacher-student relationship (standardized ß = -0.22) were significant predictors of poor subjective IAQ. In addition, school-related stress was associated with poor subjective IAQ, but only in schools without observed indoor air problem (standardized ß = -0.44).

Biomonitoring of selected persistent organic pollutants (PCDD/Fs, PCBs and PBDEs) in Finnish and Russian terrestrial and aquatic animal species.

BACKGROUND: The Finnish and Russian animal species (semi-domesticated reindeer, Finnish wild moose, Baltic grey seal and Baltic herring) samples were biomonitored in terrestrial and aquatic environments for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs). RESULTS: Grey seal (Halichoerus grypus) was clearly the most contaminated species. The mean PBDE concentration in grey seal was 115 ng/g fat, and the highest WHO-PCDD/F-PCB-TEQ (toxic equivalent set by WHO) was 327 pg/g fat. In Finnish, reindeer WHO-PCDD/F-TEQ varied from 0.92 pg/g fat in muscle to 90.8 pg/g fat in liver. WHO-PCDD/F-TEQ in moose liver samples was in the range of 0.7-4.26 pg/g fat, and WHO-PCB-TEQ in the range of 0.42-3.34 pg/g fat. Overall moose had clearly lower PCDD/F and DL-PCB concentrations in their liver than reindeer. CONCLUSIONS: Terrestrial animals generally had low POP concentrations, but in reindeer liver dioxin levels were quite high. All Finnish and Russian reindeer liver samples exceeded the EU maximum level [8] for PCDD/Fs (10 pg/g fat), which is currently set for bovine animals.

Persistent organic pollutant levels in semi-domesticated reindeer (Rangifer tarandus tarandus L.), feed, lichen, blood, milk, placenta, foetus and calf.

A study concerning persistent organic pollutants in Finnish semi-domesticated reindeer was conducted in northern Finland. The aim of this study was to explore POP presence in different tissues of reindeer. In addition, it was studied how POPs are transported from food concentrates and lichen to reindeer hind tissues and further to the placenta, foetus, milk and calf. Concentrations of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), 37 polychlorinated biphenyls (PCBs) (including 12 dioxin-like PCBs), and 15 polybrominated diphenyl ethers (PBDEs) were analysed. In most of the reindeer muscle tissue samples PCBs were clearly dominating compounds (on average 58% of the total WHO-TEQ). The total WHO-TEQ was higher in the muscle tissue of reindeer calves than in their corresponding hinds (on average 1.7 pg/g fat vs. 1.1 pg/g fat, respectively). The total WHO-TEQ concentrations were higher in the muscle and liver tissues of reindeer hinds than in their blood or placentas. The foetuses had clearly lower WHO-TEQ concentrations than their corresponding hinds. The contribution of WHO-PCDD/F-TEQ to the total WHO-TEQ was somewhat higher in the liver than in the muscle tissue. The reindeer hind-calf pair, which had gone through the lichen diet, had on average higher WHO-PCDD/F- and PCB-TEQ concentrations in their tissues than the hind-calf-pair that had gone through the reindeer food concentrate diet. WHO-PCB-TEQs in the reindeer foetuses were equal with the concentrations of placentas. The reindeer foetuses contained generally more PBDEs than their corresponding hinds and placentas. This may indicate effective transport of these compounds through the placenta of reindeer.

Lymphatic dwelling filarioid nematodes in reindeer Rangifer tarandus tarandus, (cervidae) in Finland, identified as Rumenfilaria andersoni Lankester & Snider, 1982 (nematoda: Onchocercidae: Splendidofilariinae).

A filarioid nematode inhabiting the lymphatic vessels of the subserosal rumen and mesenteries associated with a high prevalence of its microfilariae in peripheral blood was observed in Finnish reindeer (Rangifer tarandus tarandus) in 2004 and 2006. Adult specimens were collected by dissecting lymphatic vessels from slaughtered animals, where some of the nematodes were seen through the wall of the dilated vessels as thin white winding threads obscuring the vessel. The morphology of adult worms and microfilaria is described based on light and scanning electron microscopy. These filariae belong to the subfamily Splendidofilariinae of the Onchocercidae and resemble Rumenfilaria andersoni, recovered from different host and localization, the ruminal veins of Alces alces in Canada. Comparison of paratypes of this species revealed only minor differences which were not sufficient to separate the filarioid parasitic in R. tarandus in Finland and we identify the nematode as R. andersoni. However, the findings suggest two different parasite populations. The finalizing of this taxonomic question in the future requires an integrated approach, in which the DNA-based and morphological identifications are consistent.

Experiments on the ectoparasitic deer ked that often attacks humans; preferences for body parts, colour and temperature.

The deer ked (Lipoptena cervi) can fail in its host search. Host search fails when an individual deer ked irreversibly accepts a host unsuitable for its reproduction (e.g. a human) and drops its wings. In northern Europe, the main host of the deer ked is the moose (Alces alces). The deer ked is increasingly causing serious problems for humans (for example, causing deer ked dermatitis) and is considered a threat for the recreational use of forests. The adult deer ked flies in early and mid-autumn to search for a host. Our aims were: (i) to study whether there are ways to avoid deer ked attacks by wearing particular clothing, and (ii) to evaluate deer ked host choice. Using human targets, we explored the cues the deer ked uses for host selection. We studied which part of the host body deer keds target and if body colour and temperature affect their choice. In our experiments, deer keds landed more on dark and red clothing than on white clothing. Moreover, deer keds mostly attacked the upper body parts and preferred the back side of the body over the front side. Finally, deer keds preferred the warmest areas of the host.

Setaria tundra microfilariae in reindeer and other cervids in Finland.

Harmful parasites of the wild northern boreal mammals are still surprisingly poorly studied. In 2003-2006, a peritonitis outbreak caused by the filarioid nematode, Setaria tundra, emerged in Finland's reindeer population. In order to gain knowledge about the basic biology, epidemiology, and transmission dynamics of this parasite, samples for S. tundra were collected from reindeer and other cervids during the follow-up period 2004-2006. Using morphology and molecular biology methods, we describe here S. tundra's first larval stage, microfilaria (smf), for the first time scientifically. The prevalence and densities of smf were higher in reindeer calves than in adults, overall prevalence being 42%. The overall smf prevalences for moose, wild forest reindeer and roe deer were 1.4-1.8%, 23%, and 39%, respectively. The focus of microfilaremia moved north and settled down in the south simultaneously with the peritonitis outbreak. The peak microfilaremia occurred in the first summer after the infection, and smf disappeared from the blood after 2 years. Captive reindeer were smf positive over the year. The prepatent period of S. tundra was estimated to be about 4 months, and the life span at least 14 months. This parasite likely has an important impact on boreal ecosystems.

Outbreak of parasitic peritonitis in reindeer in Finland.

In 2003, there was an outbreak of peritonitis in reindeer in the southern and middle part of the Finnish reindeer herding area caused by the filarioid nematode Setaria species. In the province of Oulu, the proportion of reindeer viscera condemned owing to parasitic lesions increased from 4.9 per cent in 2001 to 40.1 per cent in 2003. In 2004, the focus of the outbreak moved approximately 100 km north. A total of 260 adult and pre-adult Setaria species nematodes were collected for morphological and molecular studies. The parasite was indistinguishable in terms of morphology and molecular biology from Setaria tundra. Samples of parasites were also collected from wild cervids. In elk, only a few cases of pre-adult encapsulated S tundra nematodes were detected on the surface of the liver but there was no peritonitis. Two roe deer had S tundra nematodes in their abdomen but no peritonitis. Of 34 wild forest reindeer, 21 had changes associated with S tundra. At meat inspection of the affected reindeer carcases, the changes observed included ascites, green fibrinous deposits, adhesions, and live and dead S tundra nematodes. There were histological lesions of granulomatous peritonitis with lymphoplasmacytic and eosinophilic infiltration. No specific bacterial growth was found. The parasitic infection had no significant effects on the pH or the organoleptic quality of the meat. There was a significant positive correlation between the worm count and the degree of peritonitis (P<0.001) and a negative correlation between the degree of peritonitis and the thickness of the back fat layer (P=0.015).

The morphology of the filaroid nematode Setaria tundra, the cause of peritonitis in reindeer Rangifer tarandus.

In Finland during 2003-2005, large numbers of nematodes, tentatively identified as Setaria sp., were observed in the peritoneal cavity of reindeer Rangifer tarandus during a peritonitis outbreak associated with poor body condition. The morphology of worms recovered from slaughtered reindeer is described based on light and scanning electron microscopy. Worms were confirmed as belonging to the superfamily Filarioidea by the presence of microfilariae-producing females and the size and the shape of the male spicules. Further classification to the genus Setaria was based on the location of worms in the peritoneal cavity and the morphology of spicules and the peribuccal crown. The present measurements correlate with those in the description of Setaria tundra by Rajewsky (1929) and only minor differences were present compared with descriptions of key parts of identification of S. yehi from the American white-tailed deer Odocoileus virginianus and mule deer O. hemionus. Current morphological findings support our earlier studies employing a polymerase chain reaction and confirm the occurrence S. tundra in reindeer in Finland.

Molecular characterization of Echinococcus isolates of cervid origin from Finland and Sweden.

The species Echinococcus granulosus is made up of several genotypic strain groups, whose taxonomical classification is still undetermined. Genotypes in the cervid-wolf life-cycle are poorly known, especially in Europe. In this study, 33 Echinococcus isolates from cervids from Finland and Sweden were characterized using mitochondrial ND1 gene sequencing. In addition, phylogenetic analysis of E. granulosus strains using the mitochondrial ATP6, ND1, ND3 and CO1 genes was performed using maximum likelihood, neighbour-joining and maximum parsimony methods. The Finnish and Swedish cervid isolates were found to represent the genotype G10. In the phylogenetic analyses, the camel (G6), pig (G7), cervid (G8) and Fennoscandian cervid (G10) strains clustered in a well-supported monophyletic group. This group differed clearly from the common sheep (G1) and horse (G4, 'E. equinus') strains, but was closely related to the cattle strain (G5, 'E. ortleppi'). Our results support the previous studies suggesting that the genotypes G6-10 should be separated from the species E. granulosus sensu stricto. However, additional morphological studies are needed, and the relationship to the cattle strain ('E. ortleppi') should be thoroughly evaluated before a final decision of the taxonomical status of the G6-10 group can be made.

Thalidomide therapy and polyneuropathy in myeloma patients.

Thalidomide is today an increasingly used therapy in advanced and refractory myeloma patients, especially in patients relapsing after high dose therapy. One important and well-known side effect of thalidomide is polyneuropathy (PNP). The purpose of this study was to investigate 1) how severe the thalidomide-induced PNP is in patients treated for myeloma 2) which neurophysiological tests and parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how neuropathic symptoms correlate with neurophysiological changes. Twelve patients received thalidomide for treatment of relapsed multiple myeloma for at least 5 months. Prior to the thalidomide treatment, all patients had been treated with chemotherapy including vincristine, and seven patients had also received cisplatin. PNP symptoms, clinical findings and neurophysiological tests before and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients had minimal and one patient slight PNP. After thalidomide treatment, 4 patients had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons were affected to some extent. Thermal thresholds were not altered, indicating that thin myelinated and unmyelinated axons are spared. The most sensitive parameter for detecting thalidomide-induced PNP was the sensory nerve compound action potential amplitude. The neuropathic symptoms deteriorated significantly during the therapy, but clinically, no patient developed a disabling PNP that would have required interrupting the therapy. The neuropathic side effects of thalidomide seem to be acceptable in myeloma patients.

Treating missing data in a clinical neuropsychological dataset--data imputation.

Missing data frequently reduce the applicability of clinically collected data in research requiring multivariate statistics. In data imputation, missing values are replaced by predicted values obtained from models based on auxiliary information. Our aim was to complete a clinical child neuropsychological data set containing 5.2% of missing observations. This was to be used in research requiring multivariate statistics. We compared four data imputation methods by artificially deleting some data. A real-donor imputation method which preserved the parameter estimates and which predicted the observed values with acceptable accuracy was used to complete the data set. In addressing the lack of studies with regard to treatment of missing data in neuropsychological data sets, this study presents information on the outcomes of applying data imputation methods to such data. The imputation modeling described can be applied to a variety of clinical neuropsychological data sets.

Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia?

OBJECTIVES: Autonomic nervous system (ANS) dysfunction and peripheral neuropathy occur in patients with chronic renal insufficiency. Adequate renal replacement therapy should prevent development or correct these abnormalities. DESIGN AND SUBJECTS: We studied retrospectively ANS and peripheral neuropathy in 32 patients with chronic uraemia who received either haemodialysis (16) or peritoneal dialysis (16) therapy, and compared the observed dialysis efficiency with changes in neurological function. METHODS: Heart rate variability (HRV) time domain indices and peripheral sensory nerve conduction studies were followed for a mean of 2.9 years. The adequacy of haemodialysis (HD) efficiency was estimated by Kt/V, an index of fractional urea clearance. Adequacy of continuous ambulatory peritoneal dialysis (CAPD) was estimated on the basis of the patient's wellbeing and nutritional status as excellent, satisfactory or poor. Based on observed changes in HRV time domain measures, the observations were divided in three subgroups: improved, unchanged or deteriorated. RESULTS: The peripheral sensory nerve conduction studies were abnormal in 38% of the patients and did not change significantly during the study. Improvement in HRV time domain measures occurred in HD patients with mean Kt/V > 1.20 or in CAPD patients with satisfactory or excellent response to dialysis treatment. Values of Kt/V < 0.85 in HD patients were associated with progressive deterioration of autonomic neuropathy. Diabetic patients (n = 4) differed from others as their HRV was grossly abnormal and did not improve. CONCLUSIONS: The adequacy of haemodialysis is a predictor of improvement of cardiac autonomic nervous function in chronic uraemia. The same trend of improvement was seen also in CAPD patients.