Additional file 1 of Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis

Additional file 1: Appendix S1. Search strategy (PubMed). Table S1. List of studies excluded at full-text screening stage. Table S2. Quality assessment of studies included in meta-analysis. Figure S1. Doi plots and LFK index for ivermectin preventive chemotherapy studies for A. lumbricoides (a), T. trichiura (b), Hookworm (c), and S. stercoralis (d). Figure S2. Doi plots and LFK index for ivermectin and albendazole preventive chemotherapy studies for Ascaris lumbricoides (a), Trichuris trichiura (b), Hookworm (c), and for all studies for Strongyloides stercoralis (d). Table S3. Pooled prevalence reduction in sensitivity analyses

Simple Nanoparticle-Based Luminometric Method for Molecular Weight Determination of Polymeric Compounds

A nanoparticle-based method utilizing time-resolved luminescence resonance energy transfer (TR-LRET) was developed for molecular weight determination. This mix-and-measure nanoparticle method is based on the competitive adsorption between the analyte and the acceptor-labeled protein to donor Eu­(III) nanoparticles. The size-dependent adsorption of molecules enables the molecular weight determination of differently sized polymeric compounds down to a concentration level of micrograms per liter. The molecular weight determination from 1 to 10 kDa for polyamino acids and from 0.3 to 70 kDa for polyethylene imines is demonstrated. The simple and cost-effective nanoparticle method as microtiter plate assay format shows great potential for the detection of the changes in molecular weight or for quantification of differently sized molecules in biochemical laboratories and in industrial polymeric processes

A Novel Mouse Model for Stable Engraftment of a Human Immune System and Human Hepatocytes

<div><p>Hepatic infections by hepatitis B virus (HBV), hepatitis C virus (HCV) and <i>Plasmodium</i> parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS) and human hepatocytes (HUHEP) in BALB/c Rag2^-/- IL-2Rγc^-/- NOD.<i>sirpa</i> uPA^tg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature <i>in vivo</i>, resulting in 20–50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months) and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.</p></div

Evaluation of circulating human hematopoietic cells in HIS and HIS-HUHEP mice.

<p>Frequency of human leukocytes (hCD45⁺) measured by FACS in the blood of (a) HIS and (B) HIS-HUHEP mice at early (10–13w) and late (19–22w) time points post-hematopoietic stem cell engraftment. Each dot represents a mouse. (C) Relative proportions of T (CD3⁺) and B (CD19⁺) cells within hCD45⁺ cells from the blood of HIS-HUHEP mice sampled longitudinally (n = 10 mice).</p

Evaluation of human immune cells and human hepatocytes in HIS-HUHEP mice.

<p>(a) Correlation analysis of the percentage of hCD45⁺ cells and hAlbumin in the blood of HIS-HUHEP mice sampled at 18–21w post-HIS and 10–16w post-HUHEP reconstitution. Each dot represents a mouse; correlation was analyzed with Pearson’s Χ² test. (B and C) Immunofluorescence analysis of intrahepatic leukocyte infiltration in (B) HIS and (C) HIS-HUHEP livers showing hCD45⁺ cells (purple) and hAlbumin⁺ cells (green). PV: portal vein, white arrows indicate hCD45⁺ cells. Nuclei are stained with DAPI (blue). Scale bar represents 100 microm.</p

Analysis of human immune cells in HIS and HIS-HUHEP mice.

<p>The (A) percentage and (B) total number of hCD45⁺ cells in the bone marrow (BM), thymus, spleen, liver and lymph nodes (LN) in HIS and HIS-HUHEP mice were determined. Absolute numbers of lymphocyte subsets in the (C) spleen and (D) liver of HIS and HIS-HUHEP mice. (E) Total human IgM and IgG concentrations were measured in the plasma of humanized mice. Error bars show standard deviation. (F) Relative proportions of CD4⁺ T_H and CD8⁺ T_C cell subsets within total CD3⁺ T cells in the liver and spleen of HIS and HIS-HUHEP mice. (G) Relative percentages of naive (CD45RA⁺ white bar) or memory (CD45RO⁺ black bar) CD3⁺ T cells in the liver and spleen of HIS and HIS-HUHEP mice. No statistically significant differences were observed between the HIS and HIS-HUHEP groups (unpaired t tests).</p

Characterization of human myeloid cells in HIS and HIS-HUHEP mice.

<p>Representative FACS contour plots of liver-isolated cells from HIS-HUHEP mice are shown for each cell subset with the parental gating strategy indicated above the plot. Total numbers of human (A) monocytes (hCD45⁺ CD3^- CD14⁺), (B) myeloid dendritic cells (hCD45⁺ CD3^- CD14^- CD11c⁺ HLA-DR⁺), and (C) plasmacytoid dendritic cells (hCD45⁺ CD3^- CD14^- CD123⁺ HLA-DR⁺) were determined in the liver and spleen of HIS and HIS-HUHEP mice. * p< 0,05 unpaired two-tailed t test.</p