Surgical Complications.

<p>BKP: Bullous Keratoplasty, PKP: Penetrating Keratoplasty.</p

Corneal Endothelial Disease.

<p>BKP: bullous keratopathy.</p

A. The ACD after DSAEK was 2.88 mm without the lenticule obstructing the anterior chamber. B. The full thickness of the cornea after DSAEK is 0.85 mm.

<p>A. The ACD after DSAEK was 2.88 mm without the lenticule obstructing the anterior chamber. B. The full thickness of the cornea after DSAEK is 0.85 mm.</p

The standard DSAEK suture pull-through technique:

<p>(A) Stripping of the Descemet membrane. (B) The donor lenticule is folded into a “taco” shape with endothelial cells enclosed. The “taco” was then placed in the Busin Glide and pulled through with forceps. (C) An anchoring 10/0 prolene stitch was placed on the donor disc at the 6 o’clock position. (D) The Busin glide was brought to the main limbal incision at the 12 o’clock position. (E) The donor lenticule disc was inserted by pulling the stitch and the disc into the anterior chamber under small flow irrigation. (F) Suturing the main incision. The donor lenticule is unfolded by increased irrigation. The anchoring prolene stitch is then cut. (G) The fluid between the lenticule and plant bed is removed and a slit lamp is used to confirm good attachment. (H) A lenticule-size bubble is injected.</p

Current Studies about DSAEK on Phakic Eyes.

*<p>ECL at 12 months postoperatively,</p>†<p>including 2 eyes that underwent cataract surgery.</p

Statistical Method for Determining and Comparing Limits of Detection of Bioassays

The current bioassay development literature lacks the use of statistically robust methods for calculating the limit of detection of a given assay. Instead, researchers often employ simple methods that provide a rough estimate of the limit of detection, often without a measure of the confidence in the estimate. This scarcity of robust methods is likely due to a realistic preference for simple and accessible methods and to a lack of such methods that have reduced the concepts of limit of detection theory to practice for the specific application of bioassays. Here, we have developed a method for determining limits of detection for bioassays that is statistically robust and reduced to practice in a clear and accessible manner geared at researchers, not statisticians. This method utilizes a four-parameter logistic curve fit to translate signal intensity to analyte concentration, which is a curve that is commonly employed in quantitative bioassays. This method generates a 95% confidence interval of the limit of detection estimate to provide a measure of uncertainty and a means by which to compare the analytical sensitivities of different assays statistically. We have demonstrated this method using real data from the development of a paper-based influenza assay in our laboratory to illustrate the steps and features of the method. Using this method, assay developers can calculate statistically valid limits of detection and compare these values for different assays to determine when a change to the assay design results in a statistically significant improvement in analytical sensitivity

DataSheet_1_Leishmania infection-induced multinucleated giant cell formation via upregulation of ATP6V0D2 expression.pdf

Leishmaniasis is caused by infection with protozoan parasites of the genus Leishmania. In both clinical and experimental visceral leishmaniasis, macrophage multinucleation is observed in parasitized tissues. However, the feature and the mechanism of macrophage multinucleation remained unclear. Here, we report that infection of Leishmania donovani, a causative agent of visceral leishmaniasis, induces multinucleation of bone marrow-derived macrophages (BMDMs) in vitro. When these infection-induced multinucleated macrophages were compared with cytokine-induced multinucleated giant cells, the former had higher phagocytic activity on red blood cells but no apparent changes on phagocytosis of latex beads. BMDMs infected with L. donovani had increased expression of ATP6V0D2, one of the components of V-ATPase, which was also upregulated in the spleen of infected mice. Infection-induced ATP6V0D2 localized in a cytoplasmic compartment, which did not overlap with the mitochondria, endoplasmic reticulum, or lysosomes. When ATP6V0D2 expression was recombinantly induced in BMDMs, the formation of multinucleated macrophages was induced as seen in the infected macrophages. Taken together, L. donovani infection induces multinucleation of macrophages via ATP6V0D2 upregulation leading to a unique metamorphosis of the macrophages toward hemophagocytes.</p

The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes

<div><p>Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near <i>BCL11A</i>, rs10830963 in <i>MTNR1B</i>, and rs2237895 in <i>KCNQ1</i> were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00), <i>P</i> = 4.42 × 10⁻²; rs10830963: 0.92 (0.85, 1.00), <i>P</i> = 4.07 × 10⁻²; rs2237895: 0.89 (0.82, 0.98), <i>P</i> = 1.29 × 10⁻²). The T2D risk alleles of rs972283 near <i>KLF14</i> contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22), <i>P</i> = 4.48 × 10⁻²), while the T2D risk allele of rs7903146 in <i>TCF7L2</i> was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90), <i>P</i> = 2.56 × 10⁻³). The T2D risk alleles of rs972283 near <i>KLF14</i> and rs11634397 near <i>ZFAND6</i> were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), <i>P</i> = 1.46 × 10⁻²; rs11634397: 1.14 (1.00, 1.29), <i>P</i> = 4.66 × 10⁻²), while the T2D risk alleles of rs780094 in <i>GCKR</i> and rs7903146 in <i>TCF7L2</i> were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), <i>P</i> = 1.35 × 10⁻⁴; rs7903146: 0.82 (0.69, 0.98), <i>P</i> = 3.18 × 10⁻²). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity (<i>P</i>_trend = 1.29 × 10⁻²) and lower waist circumference (<i>P</i> = 2.20 × 10⁻³). Genetic variants of <i>WFS1</i>, <i>CDKAL1</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>HHEX</i>, <i>KCNQ1</i>, <i>TSPAN8/LGR5</i>, <i>FTO</i>, and <i>TCF2</i> were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (<i>P</i> < 0.05). In addition, genetic variants of <i>BCL11A</i>, <i>GCKR</i>, <i>ADAMTS9</i>, <i>CDKAL1</i>, <i>KLF14</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>CDC123/CAMK1D</i>, <i>HHEX</i>, <i>MTNR1B</i>, and <i>KCNQ1</i> contributed to the risk for T2D without MetS (<i>P</i> < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation.</p></div

A proximity growth of M₃ to M₄.

<p>A proximity growth of M₃ to M₄.</p

Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes

<div><p>Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (<i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, <i>DOCK7</i>, <i>HNF1A</i>, and <i>HNF4A</i>) were genotyped. After adjusting for multiple covariates, SNPs in <i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, and <i>HNF1A</i> were identified as significantly associated with triglyceride levels in T2D patients (<i>P</i> < 0.05). The associations between the SNPs in <i>ABCA1</i> (rs3890182), <i>GCKR</i> (rs780094), and <i>BAZ1B</i> (rs2240466) remained significant even after correction for multiple testing (<i>P</i> = 8.85×10⁻³, 7.88×10⁻⁷, and 2.03×10⁻⁶, respectively). <i>BAZ1B</i> (rs2240466) also was associated with the total cholesterol level (<i>P</i> = 4.75×10⁻²). In addition, SNP rs157580 in <i>TOMM40</i> was associated with the low-density lipoprotein cholesterol level (<i>P</i> = 6.94×10⁻³). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.</p></div