Fecal Microbiota Transplants as a Treatment Option for Parkinson’s Disease

Parkinson’s disease (PD) is a progressive neurodegenerative disease with an unknown cause, high prevalence, and no effective therapy. Alterations in gut microbiota composition and function have been found in PD, which could influence the gut-brain axis. Several mechanisms have been proposed and are investigated to explain the link between gut microbiota and PD. In model systems and in individual case reports, modulation of gut microbiota has been associated with improvement of PD. A safe and effective way of gut microbiota manipulation is fecal microbiota transplant (FMT). FMT is used successfully for treatment of recurrent gastrointestinal infections as well as other indications. We advocate randomized clinical trials with FMT as a treatment option for PD

Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays

<p>Abstract</p> <p>Background</p> <p>Growing knowledge about cellular interactions in the immune system, including the central role of cytokine networks, has lead to new treatments using monoclonal antibodies that block specific components of the immune system. Systemic cytokine concentrations can serve as surrogate outcome parameters of these interventions to study inflammatory pathways operative in patients <it>in vivo</it>. This is now possible due to novel technologies such as multiplex immunoassays (MIA) that allows detection of multiple cytokines in a single sample. However, apparently trivial underappreciated processes, (sample handling and storage, interference of endogenous plasma proteins) can greatly impact the reliability and reproducibility of cytokine detection.</p> <p>Therefore we set out to investigate several processes that might impact cytokine profiles such as blood collecting tubes, duration of storage, and number of freeze thawing cycles.</p> <p>Results</p> <p>Since under physiological conditions cytokine concentrations normally are low or undetectable we spiked cytokines in the various plasma and serum samples. Overall recoveries ranged between 80-120%. Long time storage showed cytokines are stable for a period up to 2 years of storage at -80°C. After 4 years several cytokines (IL-1α, IL-1β, IL-10, IL-15 and CXCL8) degraded up to 75% or less of baseline values. Furthermore we show that only 2 out of 15 cytokines remained stable after several freeze-thawing cycles. We also demonstrate implementation of an internal control for multiplex cytokine immunoassays.</p> <p>Conclusion</p> <p>All together we show parameters which are essential for measurement of cytokines in the context of clinical trials.</p

Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia; an observational analysis

BACKGROUND: The aim of this study was to investigate the clinical outcome and especially costs of hospitalisation for community-acquired pneumonia (CAP) in relation to microbial aetiology. This knowledge is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP. METHODS: We performed our observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010. Hospital administrative databases were extracted for all resource utilisation on a patient level. Resource items were grouped in seven categories: general ward nursing, nursing on ICU, clinical chemistry laboratory tests, microbiology exams, radiology exams, medication drugs, and other.linear regression analyses were conducted to identify variables predicting costs of hospitalisation for CAP. RESULTS: Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%. Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index (indicative for severe disease), Staphylococcus aureus, or Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor. CONCLUSIONS: Median costs of hospitalisation for CAP are almost €4,000 per patient. Nursing costs are the main cause of these costs.. Apart from prevention, low-cost interventions aimed at reducing length of hospital stay therefore will most likely be cost-effective

Соціальний капітал у формуванні екстерналій освітньої сфери

У статті аналізується передавальний механізм імпульсу, який одержує економіка від зміни рівня освіти. Виходячи із припущення про прискорення (уповільнення) економічного зростання як одну із можливих екстерналій освіти, автори досліджують опосередкований вплив соціального капіталу на формування цієї екстерналії.В статье анализируется передаточный механизм импульса, полученного экономикой от изменения уровня образования. Исходя из предположения об ускорении (замедлении) экономического роста как о возможной экстерналии образования, авторы исследуют опосредованное влияние социального капитала на формирование этой экстерналии.The article under consideration analyzes the intermediary mechanism of impulse which results in economics due to education level change. In terms of assumption as regards economic growth acceleration (impairment) as one of possible education externalities the authors are researching the indirect social capital influence upon this externality formation

Romboutsia hominis sp nov., the first human gut-derived representative of the genus Romboutsia, isolated from ileostoma effluent

A Gram-stain-positive, motile, rod-shaped, obligately anaerobic bacterium, designated FRIFIT, was isolated from human ileostoma effluent and characterized. On the basis of 16S rRNA gene sequence similarity, strain FRIFIT was most closely related to the species Romboutsia ilealis CRIBT (97.7 %), Romboutsia lituseburensis DSM 797(T) (97.6 %) and Romboutsia sedimentorum LAM201(T) (96.6 %). The level of DNA-DNA relatedness between strain FRIFIT and R. ilealis CRIBT was 13.9 +/- 3.3% based on DNA-DNA hybridization. Whole genome sequence-based average nucleotide identity between strain FRIFIT and closely related Romboutsia strains ranged from 78.4-79.1 %. The genomic DNA G+C content of strain FRIFIT was 27.8 mol%. The major cellular fatty acids of strain FRIFI T were saturated and unsaturated straight-chain C12-C19 fatty acids as well as cyclopropane fatty acids, with C-16:0 being the predominant fatty acid. The polar lipid profile comprised five phospholipids and six glycolipids. These results, together with differences in phenotypic features, support the proposal that strain FRIFIT represents a novel species within the genus Romboutsia, for which the name Romboutsia hominis sp. nov. is proposed. The type strain is FRIFIT (=DSM 28814(T) = KCTC 15553(T)).Peer reviewe

Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis

BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r&gt;0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P&lt;0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P&lt;0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P&lt;0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P&lt;0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P&lt;0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P&lt;0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.Original Publication:Femke Lutgendorff, Rian M Nijmeijer, Per A Sandström, Lena M Trulsson, Karl-Eric Magnusson, Harro M Timmerman, L Paul van Minnen, Ger T Rijkers, Hein G Gooszen, Louis M A Akkermans and Johan D Söderholm, Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis., 2009, PLoS ONE, (4), 2, e4512.http://dx.doi.org/10.1371/journal.pone.0004512Licensee: Public Library of Science (PLoS)http://www.plos.org

Age-Related Immunity to Meningococcal Serogroup C Vaccination: An Increase in the Persistence of IgG2 Correlates with a Decrease in the Avidity of IgG

Contains fulltext : 97618.pdf (publisher's version ) (Open Access)Background All children and adolescents between 1 and 19 years of age in The Netherlands received a single meningococcal serogroup C conjugate (MenCC) vaccine in 2002. During follow-up 4–5 years later, the persistence of MenC polysaccharide-specific IgG was found to be dependent on age of vaccination with higher IgG levels in the oldest immunized age categories. Methods and Findings Two cross-sectional population-based serum banks, collected in 1995/1996 and in 2006/2007, were used for this study. We measured MenC polysaccharide-specific IgM, the IgG1 and IgG2 subclasses and determined the avidity of the IgG antibodies. We report that the age-related persistence of IgG after immunization with the MenCC vaccine seemed to result from an increase of IgG2 levels with age, while IgG1 levels remained stable throughout the different age-cohorts. Furthermore, an age-related increase in IgM levels was observed, correlating with the persistence of IgG antibodies with age. It is noteworthy that the increase in IgG2 correlated with a reduced IgG-avidity with age. Conclusion These date indicate that the classical characteristics of a T-cell-dependent antibody response as elicited by protein based vaccines might not be completely applicable when conjugate vaccines are administered to older children and adolescents up to 18 years of age. The response elicited by the MenCC vaccine seemed to be more a mixture of both T cell dependent and T cell independent responses in terms of humoral immunological characteristics

Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid and antibody tests up to 22 August 2020

Background: Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic. Aim: We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy. Methods: We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/ EEA). Results: Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one pointof- care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area. Conclusion: Continuous monitoring of clinical performance within more clearly defined target populations is needed.</p