Development and characterization of fluorescent dye-doped nanoparticles with enhanced fluorescence intensity and photostability [abstract]

Nanoscience Poster SessionWe report the development of fluorescent dye doped organosilicate nanoparticles (DOSNPs) synthesized from poly-methylsilsesquioxane(PMSSQ), resulting in high fluorescence intensity and excellent photostability. The surface modified DOSNPs have hydrophilic surfaces and hydrophobic cores that enhance water-solubility and protect the dyes from oxidation and phtobleaching. These DOSNPs show superior properties over conventional dyes such as high fluorescence intensity due to approximately hundred dye molecules per particle and photostability demonstrating 7% and 76% fluorescence decay under continuous excitation for rhodamine 6G (R6G) DOSNP and R6G molecules, respectively, and have potential to be used in many areas, for example, imaging, sensing and solar cells. DOSNPs, when conjugated to anti-fibronectin antibodies, increased sensitivity of detection by approximately 600 fold relative to individual dye molecules conjugated to antibody. The DOSNPs are being applied to the development of diagnostic devices to be used in the detection of drugs, metabolites and pathogens

Organosilicate nanoparticles and its applications in chem-biosensors, electronics, multifunctional coatings and textiles

This invention reports a novel technique for the rapid and cost-efficient synthesis of organosilicate nanoparticles (OSNPs) that have been successfully applied as individual building blocks for various applications. Doping these nanoparticles with fluorescent dyes results in highly fluorescent, biocompatible, water soluble nanoparticles with demonstrated long term photostability and with surface groups that can be readily used to attach various biological moieties. Fluorescent intensity of dye doped OSNPs (22.4 ± 5.3 nm) is shown to be 200 times brighter with 94% of the initial fluorescence intensity retained than the constituent dyes under continuous excitation for 10 minutes. In contrast, under identical test conditions, individual dye molecules retained only 58% of the initial fluorescence demonstrating that these nanoparticles have excellent utility in lifesciences research, forensics, chemical - biological sensors and biological imaging applications. Through our patented technology of novel bottom up fabrication technique, these nanoparticles have been used to fabricate highly porous transparent films. Optically smooth hydrophobic films with low refractive indices (as low as 1.048) and high surface areas (as high as 1325 m2/g) can be achieved on large area substrates. These unique materials can be readily interfaced with existing immunoassays in the form of inexpensive dip-stick assays for the sensitive detection of chemical and biological warfare agents or novel diagnostic strips for point of care applications. Our preliminary evaluation of these coatings in combination with dye doped OSNPs for construction of diagnostic immunoassays gave ~180 fold enhancement in fluorescence signal enhancement compared to traditional (microscope glass slide and fluorescent dye molecules) based assays. OSNPs used as filler elements within sol-gel based coatings have been shown to greatly enhance their structural stability, flexibility and wear resistance. Crack-free coatings (with thicknesses exceeding 30 microns)/novel multifunctional electrospun fibers have been successfully achieved by employing OSNP fillers (up to 75% by weight) within sol-gel compositions. POTENTIAL AREAS OF APPLICATIONS: *Chemical Biological sensors *Medical Diagnostics *Multifunctional coatings *Next generation Chemical-Biological protection textiles (Soldier technologies) PATENT STATUS: Non provisional patent application on file INVENTOR(S): Sangho Bok; Venumadhav Korampally; Luis Polo-Parada; Vamsi Mamidi; Keshab Gangopadhyay; William R. Folk; Purnendu K. Dasgupta and Shubhra Gangopadhyay CONTACT INFO: Wayne McDaniel, Ph.D.; [email protected] ; 573-884-330

Perturbations in the Urinary Exosome in Transplant Rejection

Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Ue) underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR

Mortalité néonatale au centre hospitalier universitaire de Tengandogo, Ouagadougou, Burkina Faso: une étude de cohorte retrospective: Neonatal mortality at Tengandogo University Hospital, Ouagadougou, Burkina Faso: a retrospective cohort study

Introduction: Selon l’organisation mondiale de la santé, les décès néonataux représentent 41% de la mortalité infanto-juvénile. L’Afrique subsaharienne a le taux de mortalité néonatale le plus élevé à 28‰. L’objectif de l’étude était de mesurer le taux de mortalité néonatale et d’identifier les facteurs associés au décès au Centre hospitalier universitaire de Tengandogo, Ouagadougou, Burkina Faso. Méthodes: Les nouveaux nés de 0 à 28 jours, hospitalisés entre le 1er janvier 2013 et le 31 décembre 2017 ont été inclus dans cette étude de cohorte rétrospective au service de néonatologie et de pédiatrie. Les informations ont été extraites à partir des dossiers cliniques. La survie a été estimée par la méthode de Kaplan Meier. Un modèle de Cox a permis d’identifier les facteurs associés. Résultats: Au total 641 nouveau-nés ont été inclus. Les enfants admis dès le premier jour de leur naissance représentaient 80%. La durée médiane de séjour était de 6 jours avec un intervalle interquartile de 3-12 jours. Les principaux diagnostics étaient la prématurité (36,05%), les infections néonatales (33,23%) et l’asphyxie (17,86%). Le taux de mortalité néonatale était de 22,25 pour 1000 personnes jours. Après ajustement, le poids de naissance inferieur 1500gramme (HRa = 4,13 ; IC 95% (2,58-6,67)) et la notion de réanimation à la naissance (HRa2,62 ; IC 95% [1,64-4,39)) étaient les facteurs de risque. Conclusion: Le taux de mortalité néonatale reste élevé. Le suivi prénatal, la prévention des infections, le renforcement des moyens de réanimation et la compétence des acteurs sont essentiels pour réduire ce taux. Introduction: According to the World Health Organization, neonatal deaths account for 41% of infant and child mortality. Sub-Saharan Africa has the highest neonatal mortality rate at 28‰. The objective of the study was to measure the neonatal mortality rate and identify factors associated with death at the Tengandogo University Hospital, Ouagadougou, Burkina Faso. Method: New-borns aged 0 to 28 days, hospitalised between 1 January 2013 and 31 December 2017 were included in this retrospective cohort study in the neonatology and paediatrics department. Information was extracted from clinical records. Survival was estimated by the Kaplan Meier method. A Cox model was used to identify associated factors. Results: A total of 641 new-borns were included. Children admitted on the first day of birth accounted for 80%. The median length of stay was 6 days with an interquartile range of 3-12 days. The main diagnoses were prematurity (36.05%), neonatal infections (33.23%) and asphyxia (17.86%). The neonatal mortality rate was 22.25 per 1000 person days. After adjustment, birth weight below 1500 grams (HRa = 4.13; 95% CI (2.58-6.67)) and the notion of resuscitation at birth (HRa2.62; 95% CI (1.64-4.39)) were the risk factors. Conclusion: The neonatal mortality rate remains high. Prenatal follow-up, infection prevention, strengthening of resuscitation resources and competence of actors are essential to reduce this rate

Artemisinin-based combinations versus amodiaquine plus sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali

<p>Abstract</p> <p>Background</p> <p>Because of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL) or artesunate-amodiaquine (AS+AQ) are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs.</p> <p>Methods</p> <p>From July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP), and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP), was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish new from recrudescent <it>Plasmodium falciparum </it>infections.</p> <p>Results</p> <p>397 children 6 to 59 months of age with uncomplicated <it>Plasmodium falciparum </it>malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR) were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p < 0.001); after PCR correction ACPR rates were similar among treatment groups: 95.4%, 96.9%, and 99.2% respectively (p = 0.17). Mean haemoglobin concentration increased across all treatment groups from Day 0 (9.82 ± 1.68 g/dL) to Day 28 (10.78 ± 1.49 g/dL) (p < 0.001), with the greatest improvement occurring in children treated with AQ+SP. On Day 2, the prevalence of parasitaemia was significantly greater among children treated with AQ+SP (50.8%) than in children treated with AS+AQ (10.5%) or AS+SP (10.8%) (p < 0.001). No significant difference in gametocyte carriage was found between groups during the follow-up period.</p> <p>Conclusion</p> <p>The combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated <it>P. falciparum </it>infection in Mali and appears to have the added value of longer protective effect against new infection.</p

Health care utilization among Medicare-Medicaid dual eligibles: a count data analysis

BACKGROUND: Medicare-Medicaid dual eligibles are the beneficiaries of both Medicare and Medicaid. Dual eligibles satisfy the eligibility conditions for Medicare benefit. Dual eligibles also qualify for Medicaid because they are aged, blind, or disabled and meet the income and asset requirements for receiving Supplement Security Income (SSI) assistance. The objective of this study is to explore the relationship between dual eligibility and health care utilization among Medicare beneficiaries. METHODS: The household component of the nationally representative Medical Expenditure Panel Survey (MEPS) 1996–2000 is used for the analysis. Total 8,262 Medicare beneficiaries are selected from the MEPS data. The Medicare beneficiary sample includes individuals who are covered by Medicare and do not have private health insurance during a given year. Zero-inflated negative binomial (ZINB) regression model is used to analyse the count data regarding health care utilization: office-based physician visits, hospital inpatient nights, agency-sponsored home health provider days, and total dental visits. RESULTS: Dual eligibility is positively correlated with the likelihood of using hospital inpatient care and agency-sponsored home health services and the frequency of agency-sponsored home health days. Frequency of dental visits is inversely associated with dual eligibility. With respect to racial differences, dually eligible Afro-Americans use more office-based physician and dental services than white duals. Asian duals use more home health services than white duals at the 5% statistical significance level. The dual eligibility programs seem particularly beneficial to Afro-American duals. CONCLUSION: Dual eligibility has varied impact on health care utilization across service types. More utilization of home healthcare among dual eligibles appears to be the result of delayed realization of their unmet healthcare needs under the traditional Medicare-only program rather than the result of overutilization in response to the expanded benefits of the dual eligibility program. The dual eligibility program is particularly beneficial to Asian and Afro-American duals in association with the provision of home healthcare and dental benefits

DETORQUEO, QUIRKY, and ZERZAUST Represent Novel Components Involved in Organ Development Mediated by the Receptor-Like Kinase STRUBBELIG in Arabidopsis thaliana

Intercellular signaling plays an important role in controlling cellular behavior in apical meristems and developing organs in plants. One prominent example in Arabidopsis is the regulation of floral organ shape, ovule integument morphogenesis, the cell division plane, and root hair patterning by the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB). Interestingly, kinase activity of SUB is not essential for its in vivo function, indicating that SUB may be an atypical or inactive receptor-like kinase. Since little is known about signaling by atypical receptor-like kinases, we used forward genetics to identify genes that potentially function in SUB-dependent processes and found recessive mutations in three genes that result in a sub-like phenotype. Plants with a defect in DETORQEO (DOQ), QUIRKY (QKY), and ZERZAUST (ZET) show corresponding defects in outer integument development, floral organ shape, and stem twisting. The mutants also show sub-like cellular defects in the floral meristem and in root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE MUTANT (SLM) class of genes. Molecular cloning of QKY identified a putative transmembrane protein carrying four C2 domains, suggesting that QKY may function in membrane trafficking in a Ca2+-dependent fashion. Morphological analysis of single and all pair-wise double-mutant combinations indicated that SLM genes have overlapping, but also distinct, functions in plant organogenesis. This notion was supported by a systematic comparison of whole-genome transcript profiles during floral development, which molecularly defined common and distinct sets of affected processes in slm mutants. Further analysis indicated that many SLM-responsive genes have functions in cell wall biology, hormone signaling, and various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET contribute to SUB-dependent organogenesis and shed light on the mechanisms, which are dependent on signaling through the atypical receptor-like kinase SUB

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia