Showing papers by "Charles University in Prague published in 2002"

Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening.

Abstract: Although there have been numerous reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global understanding of the population molecular genetics associated with cystic fibrosis (CF). We determined the distribution of CFTR mutations in as many regions throughout the world as possible in an effort designed to: 1) increase our understanding of ancestry-genotype relationships, 2) compare mutational arrays with disease incidence, and 3) gain insight for decisions regarding screening program enhancement through CFTR multi-mutational analyses. Information on all mutations that have been published since the identification and cloning of the CFTR gene's most common allele, DeltaF508 (or F508del), was reviewed and integrated into a centralized database. The data were then sorted and regional CFTR arrays were determined using mutations that appeared in a given region with a frequency of 0.5% or greater. Final analyses were based on 72,431 CF chromosomes, using data compiled from over 100 original papers, and over 80 regions from around the world, including all nations where CF has been studied using analytical molecular genetics. Initial results confirmed wide mutational heterogeneity throughout the world; however, characterization of the most common mutations across most populations was possible. We also examined CF incidence, DeltaF508 frequency, and regional mutational heterogeneity in a subset of populations. Data for these analyses were filtered for reliability and methodological strength before being incorporated into the final analysis. Statistical assessment of these variables revealed that there is a significant positive correlation between DeltaF508 frequency and the CF incidence levels of regional populations. Regional analyses were also performed to search for trends in the distribution of CFTR mutations across migrant and related populations; this led to clarification of ancestry-genotype patterns that can be used to design CFTR multi-mutation panels for CF screening programs. From comprehensive assessment of these data, we offer recommendations that multiple CFTR alleles should eventually be included to increase the sensitivity of newborn screening programs employing two-tier testing with trypsinogen and DNA analysis.

Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study.

Abstract: less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was �0.19 mm (95% confidence interval, �0.29 to �0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, �0.06 to 0.14 mm), with a significant difference between groups (P=.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (0.5 mm): 5% vs 14% (P = .05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups. Conclusion: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification. Arch Intern Med. 2002;162:2113-2123

Association of human aging with a functional variant of klotho

Abstract: Mice deficient in Klotho gene expression exhibit a syndrome resembling premature human aging. To determine whether variation in the human KLOTHO locus contributes to survival, we applied two newly characterized polymorphic microsatellite markers flanking the gene in a population-based association study. In a cohort chosen for its homogeneity, Bohemian Czechs, we demonstrated significant differences in selected marker allele frequencies between newborn and elderly individuals (P < 0.05). These results precipitated a search for functional variants of klotho. We identified an allele, termed KL-VS, containing six sequence variants in complete linkage disequilibrium, two of which result in amino acid substitutions F352V and C370S. Homozygous elderly individuals were underrepresented in three distinct populations: Bohemian Czechs, Baltimore Caucasians, and Baltimore African-Americans [combined odds ratio (OR) = 2.59, P < 0.0023]. In a transient transfection assay, secreted levels of klotho harboring V352 are reduced 6-fold, whereas extracellular levels of the S370 form are increased 2.9-fold. The V352/S370 double mutant exhibits an intermediate phenotype (1.6-fold increase), providing a rare example of intragenic complementation in cis by human single nucleotide polymorphisms. The remarkable conservation of F352 among homologous proteins suggests that it is functionally important. The corresponding substitution, F289V, in the closest human klotho paralog with a known substrate, cBGL1, completely eliminates its ability to cleave p-nitrophenyl-β-d-glucoside. These results suggest that the KL-VS allele influences the trafficking and catalytic activity of klotho, and that variation in klotho function contributes to heterogeneity in the onset and severity of human age-related phenotypes.

T-cell engagement of dendritic cells rapidly rearranges MHC class II transport

Abstract: Assembly of major histocompatibility complex (MHC) molecules, which present antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic reticulum; once assembled, these molecules travel from the endoplasmic reticulum to their final destination. MHC class II molecules follow a route that takes them by means of the endocytic pathway, where they acquire peptide, to the cell surface. The transport of MHC class II molecules in 'professional' antigen-presenting cells (APCs) is subject to tight control and responds to inflammatory stimuli such as lipopolysaccharide. To study class II transport in live APCs, we replaced the mouse MHC class II gene with a version that codes for a class II molecule tagged with enhanced green fluorescent protein (EGFP). The resulting mice are immunologically indistinguishable from wild type. In bone-marrow-derived dendritic cells, we observed class II molecules in late endocytic structures with transport patterns similar to those in Langerhans cells observed in situ. We show that tubular endosomes extend intracellularly and polarize towards the interacting T cell, but only when antigen-laden dendritic cells encounter T cells of the appropriate specificity. We propose that such tubulation serves to facilitate the ensuing T-cell response.

Phytoremediation of polyaromatic hydrocarbons, anilines and phenols.

Abstract: Phytoremediation technologies based on the combined action of plants and the microbial communities that they support within the rhizosphere hold promise in the remediation of land and waterways contaminated with hydrocarbons but they have not yet been adopted in large-scale remediation strategies. In this review plant and microbial degradative capacities, viewed as a continuum, have been dissected in order to identify where bottle-necks and limitations exist. Phenols, anilines and polyaromatic hydrocarbons (PAHs) were selected as the target classes of molecule for consideration, in part because of their common patterns of distribution, but also because of the urgent need to develop techniques to overcome their toxicity to human health. Depending on the chemical and physical properties of the pollutant, the emerging picture suggests that plants will draw pollutants including PAHs into the plant rhizosphere to varying extents via the transpiration stream. Mycorrhizosphere-bacteria and -fungi may play a crucial role in establishing plants in degraded ecosystems. Within the rhizosphere, microbial degradative activities prevail in order to extract energy and carbon skeletons from the pollutants for microbial cell growth. There has been little systematic analysis of the changing dynamics of pollutant degradation within the rhizosphere; however, the importance of plants in supplying oxygen and nutrients to the rhizosphere via fine roots, and of the beneficial effect of microorganisms on plant root growth is stressed. In addition to their role in supporting rhizospheric degradative activities, plants may possess a limited capacity to transport some of the more mobile pollutants into roots and shoots via fine roots. In those situations where uptake does occur (i.e. only limited microbial activity in the rhizosphere) there is good evidence that the pollutant may be metabolised. However, plant uptake is frequently associated with the inhibition of plant growth and an increasing tendency to oxidant stress. Pollutant tolerance seems to correlate with the ability to deposit large quantities of pollutant metabolites in the 'bound' residue fraction of plant cell walls compared to the vacuole. In this regard, particular attention is paid to the activities of peroxidases, laccases, cytochromes P450, glucosyltransferases and ABC transporters. However, despite the seemingly large diversity of these proteins, direct proof of their participation in the metabolism of industrial aromatic pollutants is surprisingly scarce and little is known about their control in the overall metabolic scheme. Little is known about the bioavailability of bound metabolites; however, there may be a need to prevent their movement into wildlife food chains. In this regard, the application to harvested plants of composting techniques based on the degradative capacity of white-rot fungi merits attention.

Kinetoplast DNA network: evolution of an improbable structure.

Abstract: Kinetoplast DNA (kDNA) is the most structurally complex mitochondrial DNA in nature. Unique to the single mitochondrion of unicellular flagellates of the order Kinetoplastida, kDNA is best known as a giant network of thousands of catenated circular DNAs (an electron micrograph of a network is shown

Structural aspects of high performance Mg alloys design

Abstract: Magnesium–gadolinium binary alloys exhibit good mechanical properties and high creep resistance comparable to or better than commercial WE type (Mg–Y–Nd–Zr) alloys. Combining scandium and manganese with a particular rare earth element (R.E.–Gd, Y, Ce) has a beneficial effect on the creep behaviour of complex Mg–R.E. alloys, at lower R.E. contents than in WE type alloys. They stabilise high creep resistance up to high temperatures (above 300°C) by precipitation of the stable phase Mn2Sc and by precipitation of basal plates of a Mn and R.E.-containing hexagonal phase.

Sudan I Is a Potential Carcinogen for Humans Evidence for Its Metabolic Activation and Detoxication by Human Recombinant Cytochrome P450 1A1 and Liver Microsomes

Abstract: 1-Phenylazo-2-hydroxynaphthol (Sudan I, C.I. Solvent Yellow 14) is a liver and urinary bladder carcinogen in mammals. We compared the ability of hepatic microsomal samples from different species including human to metabolize Sudan I. Comparison between experimental animals and human cytochromes P450 (CYP) is essential for the extrapolation of animal carcinogenicity data to assess human health risk. Human microsomes generated the pattern of Sudan I metabolites reproducing that formed by hepatic microsomes of rats. Using hepatic microsomes of rats pretreated with specific CYP inducers, microsomes from Baculovirus-transfected insect cells expressing recombinant human CYP enzymes, purified CYP enzymes, and selective CYP inhibitors, we found that rat CYP1A1 and recombinant human CYP1A1 are the most efficient enzymes metabolizing Sudan I. Microsomes from livers (the target of Sudan I carcinogenicity) of different human donors were used to estimate whether authentic human CYPs oxidize Sudan I. Using Western blot analysis and NH(2)-terminal sequencing, we were able to detect and quantify CYP1A1 in human hepatic microsomes. The sequence of nine amino acids of the protein band cross-reacting with antirat CYP1A1 in human microsomes, LFPISMSAT, matched the sequence of human CYP1A1 perfectly (residues 2-10). CYP1A1 expression levels varied significantly among the different human microsomes (0.04-2.4 pmol/mg protein), and constituted <0.6% of the total hepatic CYP complement. All of the human hepatic microsomal samples oxidized Sudan I to C-hydroxymetabolites. Moreover, using the nuclease P1-enhanced version of the (32)P-postlabeling assay, we found that human microsomes were competent in activating Sudan I to form adducts with DNA. The role of specific CYP enzymes in the human hepatic microsomal metabolism was investigated by correlating the CYP-catalytic activities (or CYP contents) in each microsomal sample with the levels of individual metabolites and/or Sudan I-DNA adducts formed by the same microsomes, and by examining the effects of agents that can inhibit specific CYP in Sudan I metabolism. On the basis of these studies, we attribute most of Sudan I metabolism in human microsomes to CYP1A1, but participation of CYP3A4 cannot be ruled out. These results, the first report on the metabolism of Sudan I by human CYP enzymes, strongly suggest a carcinogenic potency of this rodent carcinogen for humans.

Visual impairment and blindness in Europe and their prevention.

Abstract: The European region currently differs in many aspects, such as political, socioeconomic, and geographical. After substantial political changes at the beginning of the 1990s, the majority of central and eastern European countries started to rebuild their healthcare systems. It is apparent that eastern Europe represents a highly diverse region where the difference among countries broadens year after year. In highly industrialised countries of Europe, the leading causes of childhood serious visual loss are lesions of the central nervous system, congenital anomalies and retinal disorders. In the middle income countries of Europe, congenital cataract, glaucoma and, mainly, retinopathy of prematurity are highly expressed. The major cause of serious visual loss in adults in industrialised countries is age related macular degeneration. The other conditions comprise cataract, glaucoma, diabetic retinopathy, and uncorrected/uncorrectable refractive errors, along with low vision. In people of working age, diabetic retinopathy, retinopathy pigmentosa, and optic atrophy are the most frequently reported causes of serious visual loss. In the middle income countries of Europe, advanced cataract, glaucoma, and diabetic retinopathy are more frequently observed.

Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study.

Abstract: Rationale Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Patients Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. Results The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (±7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by ≥ 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (±12)% at 3 years being 66 (±23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (±13)%; p = 0.59. The probability of confirmed disease progression was 20 (±11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases. Conclusion Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.

Exceptional sperm cooperation in the wood mouse

Abstract: Spermatozoa from a single male will compete for fertilization of ova with spermatozoa from another male when present in the female reproductive tract at the same time. Close genetic relatedness predisposes individuals towards altruism, and as haploid germ cells of an ejaculate will have genotypic similarity of 50%, it is predicted that spermatozoa may display cooperation and altruism to gain an advantage when inter-male sperm competition is intense. We report here the probable altruistic behaviour of spermatozoa in an eutherian mammal. Spermatozoa of the common wood mouse, Apodemus sylvaticus, displayed a unique morphological transformation resulting in cooperation in distinctive aggregations or 'trains' of hundreds or thousands of cells, which significantly increased sperm progressive motility. Eventual dispersal of sperm trains was associated with most of the spermatozoa undergoing a premature acrosome reaction. Cells undergoing an acrosome reaction in aggregations remote from the egg are altruistic in that they help sperm transport to the egg but compromise their own fertilizing ability.

Progress in integrated assessment and modelling

Abstract: Environmental processes have been modelled for decades. However. the need for integrated assessment and modeling (IAM) has,town as the extent and severity of environmental problems in the 21st Century worsens. The scale of IAM is not restricted to the global level as in climate change models, but includes local and regional models of environmental problems. This paper discusses various definitions of IAM and identifies five different types of integration that Lire needed for the effective solution of environmental problems. The future is then depicted in the form of two brief scenarios: one optimistic and one pessimistic. The current state of IAM is then briefly reviewed. The issues of complexity and validation in IAM are recognised as more complex than in traditional disciplinary approaches. Communication is identified as a central issue both internally among team members and externally with decision-makers. stakeholders and other scientists. Finally it is concluded that the process of integrated assessment and modelling is considered as important as the product for any particular project. By learning to work together and recognise the contribution of all team members and participants, it is believed that we will have a strong scientific and social basis to address the environmental problems of the 21st Century.

Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study.

Abstract: The parasite Toxoplasma gondii infects 30–60% of humans worldwide. Latent toxoplasmosis, i.e., the life-long presence of Toxoplasma cysts in neural and muscular tissues, leads to prolongation of reaction times in infected subjects. It is not known, however, whether the changes observed in the laboratory influence the performance of subjects in real-life situations. The seroprevalence of latent toxoplasmosis in subjects involved in traffic accidents (N = 146) and in the general population living in the same area (N = 446) was compared by a Mantel-Haenszel test for age-stratified data. Correlation between relative risk of traffic accidents and level of anti-Toxoplasma antibody titre was evaluated with the Cochran-Armitage test for trends. A higher seroprevalence was found in the traffic accident set than in the general population (Chi2 MH = 21.45, p < 0.0001). The value of the odds ratio (OR) suggests that subjects with latent toxoplasmosis had a 2.65 (C.I.95= 1.76–4.01) times higher risk of an accident than the toxoplasmosis-negative subjects. The OR significantly increased with level of anti-Toxoplasma antibody titre (p < 0.0001), being low (OR = 1.86, C.I.95 = 1.14–3.03) for the 99 subjects with low antibody titres (8 and 16), higher (OR = 4.78, C.I.95 = 2.39–9.59) for the 37 subjects with moderate titres (32 and 64), and very high (OR = 16.03, C.I.95 = 1.89–135.66) for the 6 subjects with titres higher than 64. The subjects with latent toxoplasmosis have significantly increased risk of traffic accidents than the noninfected subjects. Relative risk of traffic accidents decreases with the duration of infection. These results suggest that 'asymptomatic' acquired toxoplasmosis might in fact represent a serious and highly underestimated public health problem, as well as an economic problem.

Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy

Abstract: Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.

Incidence of limb fracture across Europe: Results from the European prospective osteoporosis study (EPOS)

Abstract: The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study.

Abstract: Aims Direct angioplasty is an effective treatment for ST-elevation myocardial infarction. The role of very early angioplasty in non-ST-elevation infarction is not known. Thus, a randomized study of first day angiography/angioplasty vs early conservative therapy of evolving myocardial infarction without persistent ST-elevation was conducted. Methods One hundred and thirty-one patients with confirmed acute myocardial infarction without ST-segment elevations were randomized within 24h of last rest chest pain: 64 in the first day angiography/angioplasty group and 67 in the early conservative group (coronary angiography only after recurrent or stress induced myocardial ischaemia). Results All patients in the invasive group underwent coronary angiography on the day of admission (mean randomization–angiography time 6·2h). First day angioplasty of the infarct related artery was performed in 47% of the patients and bypass surgery in 35%. In the conservative group, 55% underwent coronary angiography, 10% angioplasty and 30% bypass surgery within 6 months. The primary end-point (death/reinfarction) at 6 months occurred in 6·2% vs 22·3% ( P <0·001). Six month mortality in the first day angiography/angioplasty group was 3·1% vs 13·4% in the conservative group ( P <0·03). Non-fatal reinfarction occurred in 3·1% vs 14·9% ( P <0·02). Conclusions First day coronary angiography followed by angioplasty whenever possible reduces mortality and reinfarction in evolving myocardial infarction without persistent ST-elevation, in comparison with an early conservative treatment strategy.

Antigen expression patterns reflecting genotype of acute leukemias.

Abstract: Multi-parameter flow cytometry, molecular genetics, and cytogenetic studies have all contributed to new classification of leukemia. In this review we discuss immunophenotypic characteristics of major genotypic leukemia categories. We describe immunophenotype of: B-lineage ALL with MLL rearrangements, TEL/AML1, BCR/ABL, E2A/PBX1 translocations, hyperdiploidy, and myc fusion genes; T-ALL with SCL gene aberrations and t(5;14) translocation; and AML with AML1/ETO, PML/RARα, OTT/MAL and CBFβ/MYH11 translocations, trisomies 8 or 11 and aberrations of chromosomes 7 and 5. Whereas some genotypes associate with certain immunophenotypic features, others can present with variable immunophenotype. Single molecules (as NG2, CBFβ/SMMHC and PML/RARα proteins) associated with or derived from specific translocations have been described. More often, complex immunophenotype patterns have been related to the genotype categories. Most known associations between immunophenotype and genotype have been defined empirically. Therefore, these associations should be validated in independent patient cohorts before they can be widely used for prescreening of leukemia. Progress in our knowledge on leukemia will show how the molecular–genetic changes modulate the immunophenotype as well as how the expressed protein molecules further modulate cell behavior.

Biology of the schistosome genus Trichobilharzia.

Abstract: Trichobilharzia is the largest genus within the family Schistosomatidae, covering over 40 species of avian parasites To clarify the existing confusion in the systematics of the genus, we recommend combining knowledge of life cycles and developmental stages, snail/bird hosts, cytogenetical and molecular data together with morphological criteria for the characterization of particular species The high specificity of Trichobilharzia for the intermediate host is a likely reflection of the ability to avoid the internal defence of specific snails The spectrum of final hosts (birds) seems to be much wider The infection of birds--trichobilharziasis--may lead to considerable tissue injuries, caused by eggs of the parasite or migration of immature/mature worms through the body Most Trichobilharzia (visceral species) migrate through the viscera of the host, but nasal species display a neurotropic mode of migration Due to a low specificity of penetrating cercariae, mammals (including humans) can be attacked This leads to cercarial dermatitis, predominantly in sensitized hosts Experimental infections indicate that Trichobilharzia never mature in an incompatible (mammalian) host However, not all cercariae and schistosomula are necessarily trapped and eliminated in the skin, and parasites may migrate throughout the viscera and the nervous system of mammals These findings suggest that the pathogenicity of Trichobilharzia may have been underestimated in the past and health risks associated with trichobilharziasis need to be studied further

Seasonal ecosystem variability in remote mountain lakes: implications for detecting climatic signals in sediment records

Abstract: Weather variation and climate fluctuations are the main sources of ecosystem variability in remote mountain lakes. Here we describe the main patterns of seasonal variability in the ecosystems of nine lakes in Europe, and discuss the implications for recording climatic features in their sediments. Despite the diversity in latitude and size, the lakes showed a number of common features. They were ice-covered between 5–9 months, and all but one were dimictic. This particular lake was long and shallow, and wind action episodically mixed the water column throughout the ice-free period. All lakes showed characteristic oxygen depletion during the ice-covered-period, which was greater in the most productive lakes. Two types of lakes were distinguished according to the number of production peaks during the ice-free season. Lakes with longer summer stratification tended to have two productive periods: one at the onset of stratification, and the other during the autumn overturn. Lakes with shorter stratification had a single peak during the ice-free period. All lakes presented deep chlorophyll maxima during summer stratification, and subsurface chlorophyll maxima beneath the ice. Phosphorus limitation was common to all lakes, since nitrogen compounds were significantly more abundant than the requirements for the primary production observed. The major chemical components present in the lakes showed a short but extreme dilution during thawing. Certain lake features may favour the recording of particular climatic fluctuations, for instance: lakes with two distinct productive periods, climatic fluctuations in spring or autumn (e.g., through chrysophycean cysts); lakes with higher oxygen consumption, climatic factors affecting the duration of the ice-cover (e.g., through low-oxygen tolerant chironomids); lakes with higher water retention time; changes in atmospheric deposition (e.g., through carbon or pigment burial); lakes with longer stratification, air temperature changes during summer and autumn (e.g., through all epilimnetic species).

Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study

Abstract: Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX ‘beta’ versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong’s test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more pro-active approach to identifying women at high risk of hip fracture in the community.