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

Leaf function in tropical rain forest canopy trees : the effect of light on leaf morphology and physiology in different-sized trees

In this thesis the effect of constant and fluctuating light availability on several leaf traits was studied for naturally growing trees of different sizes, i.e . from sapling to adult canopy tree, of five species in a tropical rain forest in French Guiana. Leaf acclimation responses were examined throughout the life time of leaves in order to evaluate whether leaves can profit from these adjustments in terms of carbon gain. The five species, arranged in order from most shade-tolerant to pioneer, were: Duguetia surinamensis , Vouacapoua americana , Dicorynia guianensis , Pourouma bicolor spp. digitata , and Goupia glabra .For Duguetia , Vouacapoua , Dicorynia and Goupia , it was shown that tree height and light availability had independent effects on photosynthesis and other features of leaf function. Direction and magnitude of the variation in leaf variables tended to be similar among species. The morphological variable leaf mass per unit area seemed to be a key variable as it determined most of the variation in other leaf variables.The time needed to increase the photosynthetic rate (up to 90% of its capacity) to a sudden increase in light was between 7 to 11 min for shade and sun growing saplings of Vouacapoua , Dicorynia and Pourouma . The readiness to exploit the next lightfleck was substantial in these plants as the induction loss was moderate to low, except in gap saplings of Dicorynia . The time needed to reach 75% of the maximum carboxylation efficiency (V cmax ) was used to separate the relative importance of biochemical and stomatal limitation during the time course of photosynthetic induction.The mean leaf life span of different-sized trees for Vouacapoua was 61 months (range 27-101) and for Dicorynia 32 months (range 17-54). The variation in traits in response to leaf age was low. Photosynthetic capacity and nitrogen concentration were relatively constant with time; leaf mass per unit area increased during the first 18 months. Simulations of the daily carbon gain with a low- and highlight regime showed differences among both sun- and shade-leaves and trees of different sizes. Leaf construction cost was independent of leaf life span. Leaf payback time was relatively short (4 to 40 days); it was constant during a wide range of irradiance, but increased sharply in a narrow range of low light. The rate of net return on carbon investment was slow in long-lived leaves of Vouacapoua . Leaf mass per area decreased with increased leaf life span, which could be explained by a light- and height-dependent selection pressure for leaf life span and leaf mass per area.The integration of the results with those at higher organisation levels, such as branch and tree crown, is briefly discussed, and the applicability in silvicultural systems in which light is manipulated to enhance growth and production of timber species is evaluated.Key-words: tropical rain forest, leaf morphology, photosynthesis, leaf age, tree height, shade tolerance, leaf construction costs, leaf payback time, ecophysiology.</p

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

Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide

A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth