Dried blood spots: Effects of less than optimal collection, shipping time, heat, and humidity

ObjectivesThis study investigates how factors related to collection, storage, transport time, and environmental conditions affect the quality and accuracy of analyses of dried blood spot (DBS) samples.MethodsData come from the 2016 Health and Retirement Study (HRS) DBS laboratory reports and the HRS merged with the National Climatic Data Center (NCDC) Global Historical Climate Network Daily (NCDC GHCN‐Daily) and the NCDC Local Climatological Data, by zip code. We ran regression models to examine the associations between assay values based on DBS for five analytes (total cholesterol, high‐density lipoprotein (HDL) cholesterol, glycosylated hemoglobin (HbA1c), C‐reactive protein (CRP), and cystatin C) and the characteristics of DBS cards and drops, shipping time, and temperature, and humidity at the time of collection.ResultsWe found cholesterol measures to be sensitive to many factors including small spots, shipping time, high temperature and humidity. Small spots in DBS cards are related to lower values across all analytes. Longer DBS transit time before freezing is associated with lower values of total and HDL cholesterol and cystatin C. Results were similar whether or not venous blood sample values were included in equations.ConclusionsSmall spots, long shipping time, and exposure to high temperature and humidity need to be avoided if possible. Quality of spots and cards and information on shipping time and conditions should be coded with the data to make adjustments in values when necessary. The different results across analytes indicate that results cannot be generalized to all DBS assays.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162768/2/ajhb23390_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162768/1/ajhb23390.pd

A second hit somatic (p.R905W) and a novel germline intron-mutation of TSC2 gene is found in intestinal lymphangioleiomyomatosis: a case report with literature review

Background Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis. Case presentation A nine-year-old girl with a full-blown TSC presented with abdominal masses detected during a routine check-up. Resected intestinal masses were diagnosed as LAM by thorough pathological examination. Interestingly, the LAM presented a somatic TSC2 gene mutation in exon 24 (p.R905W, c.C2713T), and the patient had intron retention by a novel germline mutation in the intron region of TSC2 (chr16:2126489, C > G). Conclusion Our case suggests that intron retention by a single nucleotide intronic mutation of TSC2 is sufficient to develop severe manifestations of TSC, but the development of LAM requires an additional somatic oncogenic mutation of TSC2.This work was supported by IITP grant funded by the Korean government (MSIP) (No.2019-0567)

Inflammatory and Immune Proteins in Umbilical Cord Blood: Association with Hearing Screening Test Failure in Preterm Neonates

Objective. We aimed to determine whether elevated levels of various inflammatory and immune proteins in umbilical cord blood are associated with an increased risk of newborn hearing screening (NHS) test failure in preterm neonates. Methods. This retrospective cohort study included 127 premature singleton infants who were born at ≤33.6 weeks. Umbilical cord plasma at birth was assayed for interleukin (IL)-6, complement C3a and C5a, matrix metalloproteinase (MMP)-9, macrophage colony-stimulating factor (M-CSF), and endostatin levels using ELISA kits. Neonatal blood C-reactive protein (CRP) levels were measured within 2 hours of birth. The primary outcome measure was a uni- or bilateral refer result on an NHS test. Univariate and multivariate analyses were applied. Results. Fifteen (11.8%) infants failed the NHS test. In the univariate analyses, high IL-6 and low C3a levels in umbilical cord plasma, funisitis, and an elevated CRP level (>5 mg/L) in the immediate postnatal period were significantly associated with NHS test failure. However, the levels of umbilical cord plasma MMP-9, C5a, M-CSF, and endostatin were not significantly different between infants who passed and those who failed the NHS test. Multiple logistic regression analyses indicated that elevated umbilical cord plasma C3a levels were independently associated with a reduced risk of NHS test failure, whereas elevated levels of umbilical cord plasma IL-6 and high CRP levels in the immediate postnatal period were significantly associated with NHS test failure. Conclusions. Our data demonstrated that in preterm neonates, a systemic fetal inflammatory response reflected by umbilical cord plasma IL-6 and immediate postnatal CRP levels may contribute to the risk for NHS test failure, whereas the changes in complement activation fragments initiated in utero may have protective effect of hearing screen failure

Proceedings of the 2003 Winter Simulation Conference

We present a system called RUBE, which allows a modeler to customize model components and model structure in 2D and 3D. RUBE employs open source tools to assist in model authoring, allowing the user to visualize models with different metaphors. For example, it is possible to visualize an event graph as a city block, or a Petri network as an organically -oriented 3D machine. We suggest that such flexibility in visualization will allow existing model types to take on forms that may be more recognizable to modeling subcommunities, while employing notation as afforded by inexpensive graphical hardware. There is also a possibility to create model types using entirely new notations

Integrative Approach toward Uncovering the Origin of Photoluminescence in Dual Heteroatom-Doped Carbon Nanodots

The pursuit of exceptionally high photoluminescence (PL) and stability is critical in the development of novel fluorophores for use in challenging bioimaging and optoelectronic devices. Carbon nanodots (CDs) doped with heteroatoms provide a particularly attractive means of effectively tailoring their intrinsic properties and exploiting new phenomena. Here, we report a one-step, scalable synthesis of boron-and-nitrogen co-doped CD (BN-CD) with outstanding optical properties unlike those of nitrogen-doped CD (N-CD) in solid state as well as solution. The detailed mechanistic framework was explored using a series of spectroscopic analyses and ultrafast spectroscopy coupled with density functional theory calculations, which all conclusively confirmed that the presence of more graphitic structures in the core and well-distributed surface states are responsible for the enhanced PL in BN-CD. Furthermore, single-molecule spectroscopy analysis demonstrated that a single BN-CD shows higher PL intensity and enhanced photobleaching time. We anticipate that this study will aid in uncovering the full potential of CDs in various fields. © 2016 American Chemical Society126251sciescopu

Integrative Approach toward Uncovering the Origin of Photoluminescence in Dual Heteroatom-Doped Carbon Nanodots

The pursuit of exceptionally high photoluminescence (PL) and stability is critical in the development of novel fluorophores for use in challenging bioimaging and optoelectronic devices. Carbon nanodots (CDs) doped with heteroatoms provide a particularly attractive means of effectively tailoring their intrinsic properties and exploiting new phenomena. Here, we report a one-step, scalable synthesis of boron-and-nitrogen co-doped CD (BN-CD) with outstanding optical properties unlike those of nitrogen-doped CD (N-CD) in solid state as well as solution. The detailed mechanistic framework was explored using a series of spectroscopic analyses and ultrafast spectroscopy coupled with density functional theory calculations, which all conclusively confirmed that the presence of more graphitic structures in the core and well-distributed surface states are responsible for the enhanced PL in BN-CD. Furthermore, single-molecule spectroscopy analysis demonstrated that a single BN-CD shows higher PL intensity and enhanced photobleaching time. We anticipate that this study will aid in uncovering the full potential of CDs in various fields.clos