Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease

The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders

Topical intranasal analgesia with EMLA for closed rhinoplasty

Background: Rhinoplasty is a traumatic procedure associated with postoperative pain. The purpose of this study is to determine the effect of topically administered intranasal EMLA 5% cream (lidocaine 25 mg/ prilocaine 25 mg) on the pain experienced in the postoperative period by patients who underwent closed rhinoplasty.Materials and methods: The study was conducted between October 2014 and May 2016 and included 66 patients divided in two groups, all of whom underwent closed rhinoplasty. In the first group (n = 33) when packaging and placing the nasal splint, each intranasal tampon (with Gelaspon) was applied with 2 ml EMLA 5% cream, and in the control group (n = 33) 2 ml Deflamol ointment was applied on each tampon. All patients were operated under general anesthesia after introduction with intravenous Propofol and maintenance of the anesthesia with Sevoflurane and opioid analgesic. After placing the patient under general anesthesia, the otorhinolaryngologist carries on with local infiltration anesthesia with a solution of lidocaine 0.5%and adrenaline 1: 100,000 4-6 ml. All patients received oral antibiotic treatment (with Klacid or Zinnat) for the period of the packaging. No corticosteroids were included in the therapeutic scheme. Post-operative pain was assessed on a visual analog scale on the 1, 3, 6, 12, 24, 48 hour in the patients of both groups.Results: The statistical analysis shows that there is a significant differencein reported results for the treatment of post-operative pain on the 1, 6 and 12 hour period in both groups studied. Four of the patients (12%) in the EMLA group had results from the VAS > 40 mm and required administration of a non-opioid analgesic in the first 24 hours, whilst in the control group this number of patients was 13 (39%).Conclusion: Intranasal application EMLA 5% cream in the packaging for reducing postoperative pain in patients who underwent closed rhinoplasty proves to be a simple and effective technique, in which we have not found adverse side effects in the study group patients despite this off label usage

Chicken egg white — characteristics of its properties and the prospects for functional foods development

The overview presents the literature data and the results of our own research on prospects of using the chicken eggs as the basis of functional foods. The composition of chicken eggs and their components, characteristics of egg white proteins properties are presented thereto. The biologically active compounds included into egg composition are analyzed. The data on the biological value of egg white are given. The characteristic of egg white foaming ability is presented. It has been shown that the ability of proteins to form stable intermolecular structures, especially with partially denaturated proteins, allows them forming viscoelastic superficial films that ensure foam stability. The high foaming ability of chicken egg protein macromolecules is directly related to their interphase properties, i. e. the ability to form interphase layers at the “liquid —  gas” interface. The foaming properties of the various egg proteins are not equal, and therefore they contribute to foaming properties at various extents. The model of egg white proteins gelation is considered and the factors influencing the gelation process are described. It has been shown that very important changes in proteins properties are caused by denaturation. The proteins lose their ability to hydrate; the protective aqueous shell around the globules disappears, the proteins stick together, grow larger and lose solubility. This process is called coagulation. The influence of denaturation and aggregation on variations of protein properties is described below. Data on protein fortification with functional ingredients (calcium, iodine, plant polyphenols) and creation of functional egg and meat foods are presented here

Working with Climate Projections to Estimate Disease Burden: Perspectives from Public Health

There is interest among agencies and public health practitioners in the United States (USA) to estimate the future burden of climate-related health outcomes. Calculating disease burden projections can be especially daunting, given the complexities of climate modeling and the multiple pathways by which climate influences public health. Interdisciplinary coordination between public health practitioners and climate scientists is necessary for scientifically derived estimates. We describe a unique partnership of state and regional climate scientists and public health practitioners assembled by the Florida Building Resilience Against Climate Effects (BRACE) program. We provide a background on climate modeling and projections that has been developed specifically for public health practitioners, describe methodologies for combining climate and health data to project disease burden, and demonstrate three examples of this process used in Florida

Intercomparison of five nets used for mesozooplankton sampling

Intercomparison of nets commonly used for mesozooplankton sampling in the Black and Mediterranean seas was attempted within SESAME (Southern European Seas: Assessing and Modelling Ecosystem Changes) project. Five nets were compared: three Juday nets equipped with 150 μm, 180 μm and 200 μm mesh size, Nansen net (100 μm mesh size) and WP2 (200 μm mesh size). Replicated samples were collected at one station in the western Black Sea offshore waters in April 2009. Collected samples were analyzed at species level (except for meroplankton), stages (for copepods) and size length. A decrease of total abundance values was observed with increasing mesh size, due to the significantly higher numbers of animals smaller than 1 mm in the samples obtained by fine mesh size than with coarser nets. Few comparisons were revealed significant for the abundance of animals with 1-2 mm length, while no significance was detected for specimens larger than 2 mm. The above differences resulted in discripancies between nets regarding species and stages composition. Biomass values did not differ significantly between nets, due to the strong contribution to total biomass of the large animals fraction (Calanus euxinus). The smallest and the largest animals revealed high variability between replicates collected by Nansen, Juday- 200 μm and WP2 nets. Correction factors were calculated for the conversion of abundance values between each couple of nets. The detected differences between nets regarding the abundance and biomass, the community taxonomic composition and size structure, as well as the estimated correction factors, provide useful information for the harmonization of data obtained by the above nets in the Black Sea

Reducing insecticide use in broad-acre grains production: An Australian study

Prophylactic use of broad-spectrum insecticides is a common feature of broad-acre grains production systems around the world. Efforts to reduce pesticide use in these systems have the potential to deliver environmental benefits to large areas of agricultural land. However, research and extension initiatives aimed at decoupling pest management decisions from the simple act of applying a cheap insecticide have languished. This places farmers in a vulnerable position of high reliance on a few products that may lose their efficacy due to pests developing resistance, or be lost from use due to regulatory changes. The first step towards developing Integrated Pest Management (IPM) strategies involves an increased efficiency of pesticide inputs. Especially challenging is an understanding of when and where an insecticide application can be withheld without risking yield loss. Here, we quantify the effect of different pest management strategies on the abundance of pest and beneficial arthropods, crop damage and yield, across five sites that span the diversity of contexts in which grains crops are grown in southern Australia. Our results show that while greater insecticide use did reduce the abundance of many pests, this was not coupled with higher yields. Feeding damage by arthropod pests was seen in plots with lower insecticide use but this did not translate into yield losses. For canola, we found that plots that used insecticide seed treatments were most likely to deliver a yield benefit; however other insecticides appear to be unnecessary and economically costly. When considering wheat, none of the insecticide inputs provided an economically justifiable yield gain. These results indicate that there are opportunities for Australian grain growers to reduce insecticide inputs without risking yield loss in some seasons. We see this as the critical first step towards developing IPM practices that will be widely adopted across intensive production systems. © 2014 Macfadyen et al

Mesenchymal Stem Cells in a Transgenic Mouse Model of Multiple System Atrophy: Immunomodulation and Neuroprotection

Mesenchymal stem cells (MSC) are currently strong candidates for cell-based therapies. They are well known for their differentiation potential and immunoregulatory properties and have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Currently there is no treatment that provides consistent long-term benefits for patients with multiple system atrophy (MSA), a fatal late onset α-synucleinopathy. Principally neuroprotective or regenerative strategies, including cell-based therapies, represent a powerful approach for treating MSA. In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP)-αsynuclein (αSYN) MSA model.MSCs were intravenously applied in aged (PLP)-αSYN transgenic mice. Behavioural analyses, defining fine motor coordination and balance capabilities as well as stride length analysis, were performed to measure behavioural outcome. Neuroprotection was assessed by quantifying TH neurons in the substantia nigra pars compacta (SNc). MSC treatment on neuroinflammation was analysed by cytokine measurements (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, GM-CSF, INFγ, MCP-1, TGF-β1, TNF-α) in brain lysates together with immunohistochemistry for T-cells and microglia. Four weeks post MSC treatment we observed neuroprotection in the SNc, as well as downregulation of cytokines involved in neuroinflammation. However, there was no behavioural improvement after MSC application.To our knowledge this is the first experimental approach of MSC treatment in a transgenic MSA mouse model. Our data suggest that intravenously infused MSCs have a potent effect on immunomodulation and neuroprotection. Our data warrant further studies to elucidate the efficacy of systemically administered MSCs in transgenic MSA models

Marine biodiversity and ecosystem function relationships: The potential for practical monitoring applications

Abstract There is an increasing demand for environmental assessments of the marine environment to include ecosystem function. However, existing schemes are predominantly based on taxonomic (i.e. structural) measures of biodiversity. Biodiversity and Ecosystem Function (BEF) relationships are suggested to provide a mechanism for converting taxonomic information into surrogates of ecosystem function. This review assesses the evidence for marine BEF relationships and their potential to be used in practical monitoring applications (i.e. operationalized). Five key requirements were identified for the practical application of BEF relationships: 1) a complete understanding of strength, direction and prevalence of marine BEF relationships, 2) an understanding of which biological components are influential within specific BEF relationships, 3) the biodiversity of the selected biological components can be measured easily, 4) the ecological mechanisms that are the most important for generating marine BEF relationships, i.e. identity effects or complementarity, are known and 5) the proportion of the overall functional variance is explained by biodiversity, and hence BEF relationships, has been established. Numerous positive and some negative BEF relationships were found within the literature, although many reproduced poorly the natural species richness, trophic structures or multiple functions of real ecosystems (requirement 1). Null relationships were also reported. The consistency of the positive and negative relationships was often low that compromised the ability to generalize BEF relationships and confident application of BEF within marine monitoring. Equally, some biological components and functions have received little or no investigation. Expert judgement was used to attribute biological components using spatial extent, presence and functional rate criteria (requirement 2). This approach highlighted the main biological components contributing the most to specific ecosystem functions, and that many of the particularly influential components were found to have received the least amount of research attention. The need for biodiversity to be measureable (requirement 3) is possible for most biological components although difficult within the functionally important microbes. Identity effects underpinned most marine BEF relationships (requirement 4). As such, processes that translated structural biodiversity measures into functional diversity were found to generate better BEF relationships. The analysis of the contribution made by biodiversity, over abiotic influences, to the total expression of a particular ecosystem function was rarely measured or considered (requirement 5). Hence it is not possible to determine the overall importance of BEF relationships within the total ecosystem functioning observed. In the few studies where abiotic factors had been considered, it was clear that these modified BEF relationships and have their own direct influence on functional rate. Based on the five requirements, the information required for immediate ‘operationalization’ of BEF relationships within marine functional monitoring is lacking. However, the concept of BEF inclusion within practical monitoring applications, supported by ecological modelling, shows promise for providing surrogate indicators of functioning