African Trypanosomes undermine humoral responses and vaccine development : link with inflammatory responses?

African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination

Monitoring response to hepatitis B and C in EU/EEA: testing policies, availability of data on care cascade and chronic viral hepatitis-related mortality – results from two surveys (2016)

Objectives: The World Health Organization (WHO) developed a European Regional Action Plan (EAP) to fast-track action towards the goal of eliminating viral hepatitis. Robust monitoring is essential to assess national programme performance. The purpose of this study was to assess the availability of selected monitoring data sources in European Union/European Economic Area (EU/EEA) Member States (MS). Methods: Availability of data sources at EU/EEA level was assessed using two surveys distributed to 31 EU/EEA MS in 2016. The two surveys covered (A) availability of policy documents on testing; testing practices and monitoring; monitoring of diagnosis and treatment initiation, and; (B) availability of data on mortality attributable to chronic viral hepatitis. Results: Just over two-thirds of EU/EEA MS responded to the surveys. 86% (18/21) reported national testing guidance covering HBV, and 81% (17/21) covering HCV; while 33% (7/21) and 38% (8/21) of countries, respectively, monitored the number of tests performed. 71% (15/21) of countries monitored the number of chronic HBV cases diagnosed and 33% (7/21) the number of people treated. Corresponding figures for HCV were 48% (10/21) and 57% (12/21). 27% (6/22) of countries reported availability of data on mortality attributable to chronic viral hepatitis. Conclusions: The results of this study suggest that sources of information in EU/EEA Member States to monitor the progress towards the EAP milestones and targets related to viral hepatitis diagnosis, cascade of care and attributable mortality are limited. Our analysis should raise awareness among EU/EEA policy makers and stimulate higher prioritisation of efforts to improve the monitoring of national viral hepatitis programmes

Heavy Schistosomiasis Associated With Poor Short-Term Memory and Slower Reaction Times in Tanzania Schoolchildren

Cross-sectional studies of the relationship between helminth infection and cognitive function can be informative in ways that treatment studies cannot. However, interpretation of results of many previous studies has been complicated by the failure to control for many potentially confounding variables.We gave Tanzanian schoolchildren aged 9±14 a battery of 11 cognitive and three educational tests and\ud assessed their level of helminth infection. We also took measurements of an extensive range of potentially confounding or mediating factors such as socioeconomic and educational factors, anthropometric and other biomedical measures. A total of 272 children were moderately or heavily\ud infected with Schistosoma haematobium, hookworm or both helminth species and 117 were uninfected with either species. Multiple regression analyses, controlling for all confounding and mediating variables, revealed that children with a heavy S. haematobium infection had signi®cantly lower scores than uninfected children on two tests of verbal short-term memory and two reaction time tasks. In one of\ud these tests the effect was greatest for children with poor nutritional status. There was no association between infection and educational achievement, nor between moderate infection with either species of helminth and performance on the cognitive tests. We conclude that children with heavy worm burdens and poor nutritional status are most likely to suffer cognitive impairment, and the domains of verbal\ud short-term memory and speed of information processing are those most likely to be affected

Alzheimer's Disease Prediction Using Longitudinal and Heterogeneous Magnetic Resonance Imaging

Recent evidence has shown that structural magnetic resonance imaging (MRI) is an effective tool for Alzheimer's disease (AD) prediction and diagnosis. While traditional MRI-based diagnosis uses images acquired at a single time point, a longitudinal study is more sensitive and accurate in detecting early pathological changes of the AD. Two main difficulties arise in longitudinal MRI-based diagnosis: (1) the inconsistent longitudinal scans among subjects (i.e., different scanning time and different total number of scans); (2) the heterogeneous progressions of high-dimensional regions of interest (ROIs) in MRI. In this work, we propose a novel feature selection and estimation method which can be applied to extract features from the heterogeneous longitudinal MRI. A key ingredient of our method is the combination of smoothing splines and the $l_1$-penalty. We perform experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The results corroborate the advantages of the proposed method for AD prediction in longitudinal studies

Zika virus: New clinical syndromes and its emergence in the western hemisphere

Zika virus (ZIKV) had remained a relatively obscure flavivirus until a recent series of outbreaks accompanied by unexpectedly severe clinical complications brought this virus into the spotlight as causing an infection of global public health concern. In this review, we discuss the history and epidemiology of ZIKV infection, recent outbreaks in Oceania and the emergence of ZIKV in the Western Hemisphere, newly ascribed complications of ZIKV infection, including Guillain-Barré syndrome and microcephaly, potential interactions between ZIKV and dengue virus, and the prospects for the development of antiviral agents and vaccines

Progress Notes : a report from the Parkinson's Disease Center at Boston University Medical Center

News and updates from the Boston University Medical Center Parkinson's Disease Cente

Progress Notes : a report from the Parkinson's Disease Center at Boston University Medical Center

News and updates from the Boston University Medical Center Parkinson's Disease Cente

Parkinson's disease: autoimmunity and neuroinflammation

Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and warrant further investigation

Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer\u27s disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of disease controls. Differential transcription was examined using RNA-seq, which allows for the examination of protein coding genes, non-coding RNAs, and splicing. Significant transcription differences specific to LOAD were observed in five genes: C10orf105, DIO2, a lincRNA, RARRES3, and WIF1. These findings were replicated in two independent publicly available microarray data sets. Network analyses, performed on 2,504 genes with moderate transcription differences in LOAD, reveal that these genes aggregate into seven networks. Two networks involved in myelination and innate immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes within the myelination network, were previously implicated in LOAD. Of the five significant genes, WIF1 and RARRES3 are directly implicated in the myelination process; the other three genes are located within the network. LOAD specific changes in DNA methylation were located throughout the genome and substantial changes in methylation were identified within the myelination network. Splicing differences specific to LOAD were observed across the genome and were decreased in all seven networks. DNA methylation had reduced influence on transcription within LOAD in the myelination network when compared to both controls. These results hint at the molecular underpinnings of LOAD and indicate several key processes, genes, and networks specific to the disease