Data_Sheet_1_Global, regional, and national burden and attributable risk factors of neurological disorders: The Global Burden of Disease study 1990–2019.docx

BackgroundNeurological disorders are a major and increasing global health challenge, which accounts for a substantial portion of the disease burden worldwide. The aim of this systematic analysis is to present the most comprehensive and up-to-date estimates of disease burden, epidemiological trends, and attributable risk factors of neurological disorders at global, regional, and national levels.MethodsWe extracted data of 18 neurological disorders from the Global Burden of Disease 2019 study database. The burden of neurological disorders was measured using the incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and further described according to age, sex, year, geographical location and socio-demographic Index (SDI). All estimates were presented with corresponding 95% uncertainty intervals (UIs).FindingsGlobally, in 2019, there were nearly 10 million deaths and 349 million DALYs due to neurological disorders. Among the 18 neurological disorders, stroke was the biggest contributor to DALYs (143232.18 [95%UI 133095.81-153241.82] in thousands) and deaths (6552.72 [95%UI 5995.20-7015.14] in thousands), followed by neonatal encephalopathy due to birth asphyxia and trauma. From 1990 to 2019, the DALYs of neurological diseases belonging to the communicable, maternal, neonatal and nutritional categories showed a sharp decrease, while Alzheimer's disease and other dementias and Parkinson's disease showed a large increase. Neurological disorders exhibited different profiles in different regions and age groups. A significant correlation between the SDI and the age-standardized DALY rates was also found except for Alzheimer's disease and other dementias. In addition, risk factors such as high systolic blood pressure, low birth weight and short gestation period, and metabolic risk contribute significantly to neurological disorders.InterpretationThe overall burden of neurological disorders has increased from 1990 to 2019, especially for non-communicable neurological disorders. The substantial variations of burden across regions emphasize the need for region-specific interventional strategies and allocation of resources based on priorities.</p

Data_Sheet_2_Global, regional, and national burden and attributable risk factors of neurological disorders: The Global Burden of Disease study 1990–2019.xlsx

BackgroundNeurological disorders are a major and increasing global health challenge, which accounts for a substantial portion of the disease burden worldwide. The aim of this systematic analysis is to present the most comprehensive and up-to-date estimates of disease burden, epidemiological trends, and attributable risk factors of neurological disorders at global, regional, and national levels.MethodsWe extracted data of 18 neurological disorders from the Global Burden of Disease 2019 study database. The burden of neurological disorders was measured using the incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and further described according to age, sex, year, geographical location and socio-demographic Index (SDI). All estimates were presented with corresponding 95% uncertainty intervals (UIs).FindingsGlobally, in 2019, there were nearly 10 million deaths and 349 million DALYs due to neurological disorders. Among the 18 neurological disorders, stroke was the biggest contributor to DALYs (143232.18 [95%UI 133095.81-153241.82] in thousands) and deaths (6552.72 [95%UI 5995.20-7015.14] in thousands), followed by neonatal encephalopathy due to birth asphyxia and trauma. From 1990 to 2019, the DALYs of neurological diseases belonging to the communicable, maternal, neonatal and nutritional categories showed a sharp decrease, while Alzheimer's disease and other dementias and Parkinson's disease showed a large increase. Neurological disorders exhibited different profiles in different regions and age groups. A significant correlation between the SDI and the age-standardized DALY rates was also found except for Alzheimer's disease and other dementias. In addition, risk factors such as high systolic blood pressure, low birth weight and short gestation period, and metabolic risk contribute significantly to neurological disorders.InterpretationThe overall burden of neurological disorders has increased from 1990 to 2019, especially for non-communicable neurological disorders. The substantial variations of burden across regions emphasize the need for region-specific interventional strategies and allocation of resources based on priorities.</p

Upregulated events related to cell-to-cell signaling and interaction, immune cell trafficking and inflammatory response.

<p>Ingenuity Pathway Analysis. The most important functional categories participating in the three major biological activities selected for localized cutaneous leishmaniasis (LCL, <i>n</i> = 5) samples are listed above for both LCL and mucosal leishmaniasis (ML, <i>n</i> = 5) groups. Only events with <i>P</i>-values higher than 0.001 were included in this list. <i># Genes</i> indicates the number of genes from each list that were involved in the events.</p

Transcriptome Patterns from Primary Cutaneous <em>Leishmania braziliensis</em> Infections Associate with Eventual Development of Mucosal Disease in Humans

<div><h3>Introduction</h3><p>Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not.</p> <h3>Methods</h3><p>Using RNA-seq, we analyzed both the human and <em>Leishmania</em> transcriptomes in primary cutaneous lesions.</p> <h3>Results</h3><p>Limited number of reads mapping to <em>Leishmania</em> transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome.</p> <h3>Conclusions</h3><p>We were able to simultaneously sequence both human and <em>Leishmania</em> mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of <em>L. braziliensis</em> infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity.</p> </div

Genes involved in the most relevant biological activities according to Ingenuity Pathway Assay.

<p>The bars indicate the significance levels of the up-regulated genes presence based on the normal event (yellow line). Black and gray bars represent LCL and ML samples, respectively. LCL: Localized Cutaneous Leishmaniasis. ML: Mucosal Leishmaniasis.</p

Genes associated with high risk for mucosal leishmaniasis progression.

<p>Genes used in Leave-One-Out cross validation analysis or selected by Ingenuity Pathway Analysis biomarker filter tools. Possible biomarkers to predict the development of mucosal leishmaniasis were determined by IPA analysis and have a significant fold change and a predicted importance due to their use as diagnostic and prognostic biomarkers in other diseases.</p><p>FC: fold change. NE: No expressed.</p

Global transcriptional expression patterns.

<p>Hierarchical clustering was performed using the Euclidean distance method (Gene Cluster 3.0) with complete linkage for both samples and genes assays. Intensity of gene expression increases from black to yellow. The heat map in the left panel includes the 18,577 genes detected by RNA-seq and shows that the samples were correctly clustered into the two clinical phenotypic groups, ML and LCL. The right panel represents the same assay using the 1208 genes selected by the dimensional reduction step performed by the <i>t-test</i>, confirming that the samples could still be clustered into LCL and ML groups. LCL: Localized Cutaneous Leishmaniasis. ML: Mucosal Leishmaniasis.</p

Binding affinity of aptamers GBM128 and GBM131 to trypsin or proteinase K treated U118-MG cells.

<p>After 2 min and 10 min trypsin or proteinase K treatment, the binding of GBM128 and GBM131 was apparently affected by trypsin digestion but totally quenched by proteinase K. The final concentration of FAM-labeled aptamers was 250 nM.</p

Using the selected aptamers to recognize FFPE normal or glioma tissue sections.

<p>FFPE tissue sections were incubated with cy5-labeled aptamers. A =  Normal brain tissue with GBM128; B =  Glioblastoma tissue with GBM128; C =  Anaplastic oligodendroglima with GBM128; D =  Oligoastrocytoma with GBM128; E =  Pilocytic astrocytoma with GBM128; F =  Normal brain tissue with GBM131; G =  Glioblastoma tissue with GBM131; H =  Anaplastic oligodendroglima with GBM131; I =  Oligoastrocytoma with GBM131; J =  Pilocytic astrocytoma with GBM131. The final concentration of Cy5-labeled aptamers was 250 nM.</p

Top 10 biological pathways observed in American tegumentary leishmaniasis lesions based on clinical presentation.

<p>Assay using Ingenuity Pathway Analysis for gene classification according to functional annotation. Biological activities were ordered according to <i>P</i>-values. <i># Genes</i> indicates the number of genes from each list that were involved in the biological activity.</p