Impact of solid waste disposal on nutrient dynamics in a sandy catchment

Groundwaters impacted by mature landfill leachate are generally enriched in ammonium. In order to assess the dynamics of ammonium exchanges between leachates and the water system inside a sandy permeable catchment we measured ammonium, nitrate and chloride concentrations in the stream and in sediment pore waters of the streambed of a landfill impacted aquifer. Geophysical investigation methods complemented the biogeochemical survey. The studied zone is a 23 km² catchment located in a coastal lagoon area sensitive to eutrophication risk. Ammonium concentrations in the river were up to 800 µmol l−1 during low water period in summer. Three surveys of the river chemistry showed a regular increase in ammonium, nitrate and chloride concentrations along a 1 km section of the watercourse, downstream the landfill, implying that the leachate plume exfiltrates along this section. Sediment cores collected within this section showed all an increase in ammonium concentrations with depth in pore waters as a consequence of the landfill leachate dispersion, as attested by a simultaneous increase in chloride concentrations. Nitrate enrichment in the river water was due to nitrification of ammonium at the interface between groundwater and streamwater. The apparent nitrification rate obtained was within values reported for turbid estuaries, although the river contained very little suspended particulate matter. Actually, pore water chemistry suggests that nitrification occurred for the most part in subsurface permeable sediments, rather than in stream water. The overall topographic, hydrological, geochemical, and geoelectrical data set permit to estimate the extension of the chloride and ammonium plume. The estimation of the apparent ammonium plume velocity is 23 m year−1 whereas the chloride plume velocity should be 50 m year−1. The river is the outlet of the impacted groundwaters. Considering that the input of ammonium from the landfill is balanced by the present day output via the river, the residence time of ammonium in the aquifer is between 7 and 18 years

The effect of physical therapy treatment in patients with subjective tinnitus:A systematic review

Background: Tinnitus is a very common symptom that often causes distress and decreases the patient's quality of life. Apart from the well-known causes, tinnitus can in some cases be elicited by dysfunctions of the cervical spine or the temporomandibular joint (TMJ). To date however, it is unclear whether alleviation of these dysfunctions, by physical therapy treatment, also decreases the tinnitus complaints. Such physical therapy could be an interesting treatment option for patients that are now often left without treatment. Objectives: The aim of this review was to investigate the current evidence regarding physical therapy treatment in patients with tinnitus. Data sources: The online databases Pubmed, Web of Science, Cochrane, and Embase were searched up to March 2016. Two independent reviewers conducted the data extraction and methodological quality assessment. Study eligibility criteria: Only randomized controlled trials and quasi-experimental trials were included in the review. Studies had to be written in English, French, Dutch, or German. Participants and interventions: The included studies investigated the effect of physical therapy treatment modalities on tinnitus severity in patients suffering from subjective tinnitus. Results: Six studies were included in this review, four investigating cervical spine treatment and two investigating TMJ treatment. These studies show positive effects of cervical spine treatment (manipulations, exercises, triggerpoint treatment) on tinnitus severity. Additionally, decrease in tinnitus severity and intensity was demonstrated after TMJ treatment, following splints, occlusal adjustments as well as jaw exercises. Limitations: The risk of bias in the included studies was high, mainly due to lack of randomization, lack of blinding of subjects, therapists, and/or investigators. Additionally, risk of bias is present due to incomplete presentation of the data and selective reporting. A major issue of the reviewed papers is the heterogeneity of the included study populations, treatments and outcome measures, which inhibit data pooling and meta-analysis. Conclusions: Despite the methodological issues in the included studies and the consequent low quality evidence, it is noteworthy that all included studies show positive treatment effects. Before recommendations can be made, these results need to be confirmed in larger, high quality studies, using unambiguous inclusion criteria, state-of-the-art treatment, and high quality outcome measures

Relationship of faecal calprotectin and long-term outcomes in Finnish patients with Crohn's disease : retrospective multi-centre chart review study

Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (+/- 2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed. Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test. Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 mu g/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FCPeer reviewe

ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants

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Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11 C]UCB-J Positron Emission Tomography Study

BACKGROUND: Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and is strongly related to functional deficits. OBJECTIVE: In this longitudinal observational study, we determine the rate at which synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and we test the relationship with disease progression. METHODS: Our cross-sectional cohort included 32 participants with probable PSP and 16 with probable CBD (all amyloid-negative corticobasal syndrome), recruited from tertiary care centers in the United Kingdom, and 33 sex- and age-matched healthy control subjects. Synaptic density was estimated by positron emission tomography imaging with the radioligand [11 C]UCB-J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [11 C]UCB-J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty-two participants with PSP/CBD had a follow-up [11 C]UCB-J positron emission tomography scan after 1 year. We calculated the annualized change in [11 C]UCB-J nondisplaceable binding potential and correlated this with the change in clinical severity. RESULTS: We found significant annual synaptic loss within the frontal lobe (-3.5%, P = 0.03) and the right caudate (-3.9%, P = 0.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (R = 0.47, P = 0.03) and cognition (Addenbrooke's Cognitive Examination-Revised, R = -0.62, P = 0.003). CONCLUSIONS: We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early-phase clinical trials of disease-modifying treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (µMT) and IgM-deficient (IgM−/−) mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei–infected µMT and IgM−/− mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in µMT mice as well as in IgM−/− mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection

Claudin 13, a Member of the Claudin Family Regulated in Mouse Stress Induced Erythropoiesis

Mammals are able to rapidly produce red blood cells in response to stress. The molecular pathways used in this process are important in understanding responses to anaemia in multiple biological settings. Here we characterise the novel gene Claudin 13 (Cldn13), a member of the Claudin family of tight junction proteins using RNA expression, microarray and phylogenetic analysis. We present evidence that Cldn13 appears to be co-ordinately regulated as part of a stress induced erythropoiesis pathway and is a mouse-specific gene mainly expressed in tissues associated with haematopoietic function. CLDN13 phylogenetically groups with its genomic neighbour CLDN4, a conserved tight junction protein with a putative role in epithelial to mesenchymal transition, suggesting a recent duplication event. Mechanisms of mammalian stress erythropoiesis are of importance in anaemic responses and expression microarray analyses demonstrate that Cldn13 is the most abundant Claudin in spleen from mice infected with Trypanosoma congolense. In mice prone to anaemia (C57BL/6), its expression is reduced compared to strains which display a less severe anaemic response (A/J and BALB/c) and is differentially regulated in spleen during disease progression. Genes clustering with Cldn13 on microarrays are key regulators of erythropoiesis (Tal1, Trim10, E2f2), erythrocyte membrane proteins (Rhd and Gypa), associated with red cell volume (Tmcc2) and indirectly associated with erythropoietic pathways (Cdca8, Cdkn2d, Cenpk). Relationships between genes appearing co-ordinately regulated with Cldn13 post-infection suggest new insights into the molecular regulation and pathways involved in stress induced erythropoiesis and suggest a novel, previously unreported role for claudins in correct cell polarisation and protein partitioning prior to erythroblast enucleation