Influence of Drug-Carrier Polymers on Alpha-Synucleinopathies: A Neglected Aspect in New Therapies Development.

Current therapeutic strategies to treat neurodegenerative diseases, such as alpha-synucleinopathies, aim at enhancing the amount of drug reaching the brain. Methods proposed, such as intranasal administration, should be able to bypass the blood brain barrier (BBB) and even when directly intracerebrally injected they could require a carrier to enhance local release of drugs. We have investigated the effect of a model synthetic hydrogel to be used as drug carrier on the amount of alpha-synuclein aggregates in cells in culture. The results indicated that alpha-synuclein aggregation was affected by the synthetic polymer, suggesting the need for testing the effect of any used material on the pathological process before its application as drug carrier.Peer Reviewe

Dark Heritage

Peer reviewe

An integrated MCDM approach to evaluate public transportation systems in Tehran

Public transportation is one of the most important systems in transportation, especially in big and crowded cities. As a result, evaluation of public transportation systems is a strategic decision-making problem for both private and public sections. In this paper, the problem of public transportation passengers in Tehran is addressed and their satisfaction levels are assessed by using passenger satisfaction survey. An integrated MCDM approach is proposed for evaluation of public transportation systems based on Delphi method, group analytic hierarchy process (GAHP) and preference ranking organization method for enrichment of evaluations (PROMETHEE). The proposed model provides more reliable and realistic results and introduces directions for future improvements of public transportation service quality. A sensitivity analysis is applied to investigate the influence of criteria weights on the decision making problem. As a conclusion, the most important public transportation systems in Tehran orderly are: metro, taxi, BRT, bus and van. Therefore, Tehran Municipality and policy makers should encourage and support the previously mentioned systems

Waist circumference, abdominal obesity, and depression among overweight and obese U.S. adults: national health and nutrition examination survey 2005-2006

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with an increased risk of mental illness; however, evidence linking body mass index (BMI)-a measure of overall obesity, to mental illness is inconsistent. The objective of this study was to examine the association of depressive symptoms with waist circumference or abdominal obesity among overweight and obese U.S. adults.</p> <p>Methods</p> <p>A cross-sectional, nationally representative sample from the 2005-2006 National Health and Nutrition Examination Survey was used. We analyzed the data from 2,439 U.S. adults (1,325 men and 1,114 nonpregnant women) aged ≥ 20 years who were either overweight or obese with BMI of ≥ 25.0 kg/m². Abdominal obesity was defined as waist circumference of > 102 cm for men and > 88 cm for women. Depressive symptoms (defined as having major depressive symptoms or moderate-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having major depressive symptoms and moderate-to-severe depressive symptoms were estimated using logistic regression analysis.</p> <p>Results</p> <p>After multivariate adjustment for demographics and lifestyle factors, waist circumference was significantly associated with both major depressive symptoms (OR: 1.03, 95% CI: 1.01-1.05) and moderate-to-severe depressive symptoms (OR: 1.02, 95% CI: 1.01-1.04), and adults with abdominal obesity were significantly more likely to have major depressive symptoms (OR: 2.18, 95% CI: 1.35-3.59) or have moderate-to-severe depressive symptoms (OR: 2.56, 95% CI: 1.34-4.90) than those without. These relationships persisted after further adjusting for coexistence of multiple chronic conditions and persisted in participants who were overweight (BMI: 25.0-< 30.0 kg/m²) when stratified analyses were conducted by BMI status.</p> <p>Conclusion</p> <p>Among overweight and obese U.S. adults, waist circumference or abdominal obesity was significantly associated with increased likelihoods of having major depressive symptoms or moderate-to-severe depressive symptoms. Thus, mental health status should be monitored and evaluated in adults with abdominal obesity, particularly in those who are overweight.</p

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) : characterisation of a novel cerebropulmonary disease

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.Peer reviewe

Use of twitter data for waste minimisation in beef supply chain

Approximately one third of the food produced is discarded or lost, which accounts for 1.3 billion tons per annum. The waste is being generated throughout the supply chain viz. farmers, wholesalers/processors, logistics, retailers and consumers. The majority of waste occurs at the interface of retailers and consumers. Many global retailers are making efforts to extract intelligence from customer’s complaints left at retail store to backtrack their supply chain to mitigate the waste. However, majority of the customers don’t leave the complaints in the store because of various reasons like inconvenience, lack of time, distance, ignorance etc. In current digital world, consumers are active on social media and express their sentiments, thoughts, and opinions about a particular product freely. For example, on an average, 45,000 tweets are tweeted daily related to beef products to express their likes and dislikes. These tweets are large in volume, scattered and unstructured in nature. In this study, twitter data is utilised to develop waste minimization strategies by backtracking the supply chain. The execution process of proposed framework is demonstrated for beef supply chain. The proposed model is generic enough and can be applied to other domains as well

The Complete Genome Sequence of the Pathogenic Intestinal Spirochete Brachyspira pilosicoli and Comparison with Other Brachyspira Genomes

Background: The anaerobic spirochete Brachyspira pilosicoli colonizes the large intestine of various species of birds and mammals, including humans. It causes ''intestinal spirochetosis'', a condition characterized by mild colitis, diarrhea and reduced growth. This study aimed to sequence and analyse the bacterial genome to investigate the genetic basis of its specialized ecology and virulence. Methodology/Principal Findings: The genome of B. pilosicoli 95/1000 was sequenced, assembled and compared with that of the pathogenic Brachyspira hyodysenteriae and a near-complete sequence of Brachyspira murdochii. The B. pilosicoli genome was circular, composed of 2,586,443 bp with a 27.9 mol% G+C content, and encoded 2,338 genes. The three Brachyspira species shared 1,087 genes and showed evidence of extensive genome rearrangements. Despite minor differences in predicted protein functional groups, the species had many similar features including core metabolic pathways. Genes distinguishing B. pilosicoli from B. hyodysenteriae included those for a previously undescribed bacteriophage that may be useful for genetic manipulation, for a glycine reductase complex allowing use of glycine whilst protecting from oxidative stress, and for aconitase and related enzymes in the incomplete TCA cycle, allowing glutamate synthesis and function of the cycle during oxidative stress. B. pilosicoli had substantially fewer methyl-accepting chemotaxis genes than B. hyodysenteriae and hence these species are likely to have different chemotactic responses that may help to explain their different host range and colonization sites. B. pilosicoli lacked the gene for a new putative hemolysin identified in B. hyodysenteriae WA1. Both B. pilosicoli and B. murdochii lacked the rfbBADC gene cluster found on the B. hyodysenteriae plasmid, and hence were predicted to have different lipooligosaccharide structures. Overall, B. pilosicoli 95/1000 had a variety of genes potentially contributing to virulence. Conclusions/Significance: The availability of the complete genome sequence of B. pilosicoli 95/1000 will facilitate functional genomics studies aimed at elucidating host-pathogen interactions and virulence

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample

<p>Abstract</p> <p>Background</p> <p>People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample.</p> <p>Methods</p> <p>In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease.</p> <p>Results</p> <p>Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, <it>p </it>= .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, <it>p </it>< .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, <it>p </it>= .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, <it>p </it>= .011), independent of lifestyle factors and confounders.</p> <p>Conclusions</p> <p>Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.</p

Challenges of adapting English médium instruction into the Spanish university curricula and some novel solutions

The integration of the Spanish university system in the European Higher Education Area (EHEA) demands a series of concrete proposals. As we advance in the implementation of the process of Bologna, it is necessary to contemplate a new paradigm of teaching/learning. Central to this new paradigm is the adaptation of the curricula into the English language medium (EMI). Among many strategies for internationalization of the Universidad Politécnica de Madrid (UPM) under adoption, this university has funded a project TechEnglish intends to facilitate the conversion of subjects and eventually degree programs into the delivery in the English Language. This paper details a work in progress and describes the collaboration between content teachers and applied linguistics. The three collaborative actions are currently underway: observation of classes by applied linguists, seminar delivery on topics requested by the content teachers, and materials development with the help of teaching assistants. We are convinced that this collaboration is the necessary ingredient to promote teaching and learning through English at our university