42 research outputs found

    Mobile phone based mini-spectrometer for rapid screening of skin cancer

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    We demonstrate a highly sensitive mobile phone based spectrometer that has potential to detect cancerous skin lesions in a rapid, non-invasive manner. Earlier reports of low cost spectrometers utilize the camera of the mobile phone to image the field after moving through a diffraction grating. These approaches are inherently limited by the closed nature of mobile phone image sensors and built in optical elements. The system presented uses a novel integrated grating and sensor that is compact, accurate and calibrated. Resolutions of about 10 nm can be achieved. Additionally, UV and visible LED excitation sources are built into the device. Data collection and analysis is simplified using the wireless interfaces and logical control on the smart phone. Furthermore, by utilizing an external sensor, the mobile phone camera can be used in conjunction with spectral measurements. We are exploring ways to use this device to measure endogenous fluorescence of skin in order to distinguish cancerous from non-cancerous lesions with a mobile phone based dermatoscope

    Multiomic immune clockworks of pregnancy

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    Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core. Consequently, a precise understanding of these chronologically paced immune adaptations and of the biological pacemakers that synchronize the pregnancy “immune clock” is a critical first step towards identifying deviations that are hallmarks of peterm birth. Here, we will review key elements of the fetal, placental, and maternal pacemakers that program the immune clock of pregnancy. We will then emphasize multiomic studies that enable a more integrated view of pregnancy-related immune adaptations. Such multiomic assessments can strengthen the biological plausibility of immunological findings and increase the power of biological signatures predictive of preterm birth

    Multiomics Longitudinal Modeling of Preeclamptic Pregnancies

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    Preeclampsia is a complex disease of pregnancy whose physiopathology remains unclear and that poses a threat to both mothers and infants. Specific complex changes in women\u27s physiology precede a diagnosis of preeclampsia. Understanding multiple aspects of such a complex changes at different levels of biology, can be enabled by simultaneous application of multiple assays. We developed prediction models for preeclampsia risk by analyzing six omics datasets from a longitudinal cohort of pregnant women. A machine learning-based multiomics model had high accuracy (area under the receiver operating characteristics curve (AUC) of 0.94, 95% confidence intervals (CI):[0.90, 0.99]). A prediction model using only ten urine metabolites provided an accuracy of the whole metabolomic dataset and was validated using an independent cohort of 16 women (AUC= 0.87, 95% CI:[0.76, 0.99]). Integration with clinical variables further improved prediction accuracy of the urine metabolome model (AUC= 0.90, 95% CI:[0.80, 0.99], urine metabolome, validated). We identified several biological pathways to be associated with preeclampsia. The findings derived from models were integrated with immune system cytometry data, confirming known physiological alterations associated with preeclampsia and suggesting novel associations between the immune and proteomic dynamics. While further validation in larger populations is necessary, these encouraging results will serve as a basis for a simple, early diagnostic test for preeclampsia

    Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

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    Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB

    Pompe disease diagnosis and management guideline

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    ACMG standards and guidelines are designed primarily as an educational resource for physicians and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. in determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.Duke Univ, Med Ctr, Durham, NC 27706 USAOregon Hlth Sci Univ, Portland, OR 97201 USANYU, Sch Med, New York, NY USAUniv Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32611 USAIndiana Univ, Bloomington, in 47405 USAUniv Miami, Miller Sch Med, Coral Gables, FL 33124 USAHarvard Univ, Childrens Hosp, Sch Med, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, São Paulo, BrazilColumbia Univ, New York, NY 10027 USANYU, Bellevue Hosp, Sch Med, New York, NY USAColumbia Univ, Med Ctr, New York, NY 10027 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

    Study of PM2.5 oxidative potential and oxidative stress in bronchial epithelial BEAS-2B cells

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    La pollution atmosphérique par les particules en suspension « PM » dans l’air constitue une préoccupation actuelle majeure en raison de ses effets délétères sur la santé humaine. Aujourd’hui, un manque de connaissances demeure vis-à-vis du rôle spécifique de certains constituants des particules et des différentes fractions des PM sur l’apparition du stress oxydant. La capacité des PM à déclencher la production d’espèces réactives de l’oxygène (ERO) en cause dans le stress oxydant peut également être renseignée par des méthodes chimiques de potentiel oxydant. Cette thèse vise à étudier le potentiel oxydant et le stress oxydant induit par les différentes fractions d’échantillons de particules PM₂,₅ collectées sur des sites de typologies urbaine, trafic routier et industrielle. Le potentiel oxydant (OP) a été évalué par la mesure de la vitesse d'oxydation de l’acide ascorbique (AA) et du dithiothréitol (DTT). Il a été montré que les deux tests de potentiel apportaient des informations complémentaires, OP-AA normalisé au volume étant relié aux concentrations de PM₂,₅ et aux sources de combustion, tandis que OP-DTT s’avère être sensible aux sources de particules émettant des métaux. Le stress oxydant a été étudié en quantifiant les ERO, les atteintes oxydatives aux protéines (protéines carbonylées), à la membrane plasmique (8-isoprostane) et à l’ADN (8-OHdG). Les particules totales sont capables d'induire la surproduction des ERO et de causer des dommages aux protéines, à des niveaux plus élevés que les autres fractions. Des altérations plus grandes de la membrane plasmique et de l’ADN ont été constatées avec la fraction particulaire et les extraits organiques des échantillons de PM₂,₅-₀,₃ provenant du site urbain. Il n’a pas été trouvé de corrélation entre le potentiel oxydant et les dommages oxydatifs aux macromolécules biologiques, ce qui signifie que ces mesures de OP ne permettraient pas de prédire les dommages cellulaires in vitro que nous avons suivis dans cette étude. Une approche plus globale, considérant notamment la mobilisation du système anti-oxydant dans la réponse cellulaire, pourrait permettre de mieux appréhender l’apport de la mesure du potentiel oxydant dans la compréhension des effets des PM en lien avec le stress oxydant cellulaire.Air pollution by airborne particulate matter (PM) is a current major concern because of its harmful effect on human health. Nowadays, a lack of knowledge remains regarding the specific role of certain PM components, and the different PM fractions on the occurrence of oxidative stress. The ability of PM to trigger the production of reactive oxygen species (ROS) involved in oxidative stress can also be assessed by chemical methods of oxidative potential (OP). This thesis aims at studying the oxidative potential and the oxidative stress induced by the different fractions of PM₂,₅ samples collected in urban, traffic, and industrial sites. OP was evaluated by measuring the depletion rate of ascorbic acid (AA) and dithiothreitol (DTT). Both tests were shown to provide complementary information, with volume normalized OP-AA being related to PM₂,₅ concentrations and combustion sources, while OP-DTT was found to be sensitive to metal-emitting particle sources. Oxidative stress was studied by quantifying ROS, oxidative damage to proteins (carbonyl proteins), cell membrane (8-isoprostane) and DNA (8-OHdG). Total particles are capable of inducing ROS overproduction, causing damage to proteins, at higher levels than other fractions. Higher cell membrane damage and DNA damage were found with the particulate fraction and organic extracts of PM₂,₅-₀,₃ samples from the urban site. No correlation was found between oxidative potential and oxidative damage to biological macromolecules, which means that these OP measurements are not predictive of the in vitro cellular damages that were followed in this study. A more global approach, considering the mobilization of the antioxidant system in the cellular response, could allow a better understanding of the contribution of the oxidative potential in the understanding of PM effects, in relation to cellular oxidative stress

    Etude du potentiel oxydant des PM2,5 et du stress oxydant induit sur les cellules épithéliales bronchiques BEAS-2B

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    Air pollution by airborne particulate matter (PM) is a current major concern because of its harmful effect on human health. Nowadays, a lack of knowledge remains regarding the specific role of certain PM components, and the different PM fractions on the occurrence of oxidative stress. The ability of PM to trigger the production of reactive oxygen species (ROS) involved in oxidative stress can also be assessed by chemical methods of oxidative potential (OP). This thesis aims at studying the oxidative potential and the oxidative stress induced by the different fractions of PM₂,₅ samples collected in urban, traffic, and industrial sites. OP was evaluated by measuring the depletion rate of ascorbic acid (AA) and dithiothreitol (DTT). Both tests were shown to provide complementary information, with volume normalized OP-AA being related to PM₂,₅ concentrations and combustion sources, while OP-DTT was found to be sensitive to metal-emitting particle sources. Oxidative stress was studied by quantifying ROS, oxidative damage to proteins (carbonyl proteins), cell membrane (8-isoprostane) and DNA (8-OHdG). Total particles are capable of inducing ROS overproduction, causing damage to proteins, at higher levels than other fractions. Higher cell membrane damage and DNA damage were found with the particulate fraction and organic extracts of PM₂,₅-₀,₃ samples from the urban site. No correlation was found between oxidative potential and oxidative damage to biological macromolecules, which means that these OP measurements are not predictive of the in vitro cellular damages that were followed in this study. A more global approach, considering the mobilization of the antioxidant system in the cellular response, could allow a better understanding of the contribution of the oxidative potential in the understanding of PM effects, in relation to cellular oxidative stress.La pollution atmosphérique par les particules en suspension « PM » dans l’air constitue une préoccupation actuelle majeure en raison de ses effets délétères sur la santé humaine. Aujourd’hui, un manque de connaissances demeure vis-à-vis du rôle spécifique de certains constituants des particules et des différentes fractions des PM sur l’apparition du stress oxydant. La capacité des PM à déclencher la production d’espèces réactives de l’oxygène (ERO) en cause dans le stress oxydant peut également être renseignée par des méthodes chimiques de potentiel oxydant. Cette thèse vise à étudier le potentiel oxydant et le stress oxydant induit par les différentes fractions d’échantillons de particules PM₂,₅ collectées sur des sites de typologies urbaine, trafic routier et industrielle. Le potentiel oxydant (OP) a été évalué par la mesure de la vitesse d'oxydation de l’acide ascorbique (AA) et du dithiothréitol (DTT). Il a été montré que les deux tests de potentiel apportaient des informations complémentaires, OP-AA normalisé au volume étant relié aux concentrations de PM₂,₅ et aux sources de combustion, tandis que OP-DTT s’avère être sensible aux sources de particules émettant des métaux. Le stress oxydant a été étudié en quantifiant les ERO, les atteintes oxydatives aux protéines (protéines carbonylées), à la membrane plasmique (8-isoprostane) et à l’ADN (8-OHdG). Les particules totales sont capables d'induire la surproduction des ERO et de causer des dommages aux protéines, à des niveaux plus élevés que les autres fractions. Des altérations plus grandes de la membrane plasmique et de l’ADN ont été constatées avec la fraction particulaire et les extraits organiques des échantillons de PM₂,₅-₀,₃ provenant du site urbain. Il n’a pas été trouvé de corrélation entre le potentiel oxydant et les dommages oxydatifs aux macromolécules biologiques, ce qui signifie que ces mesures de OP ne permettraient pas de prédire les dommages cellulaires in vitro que nous avons suivis dans cette étude. Une approche plus globale, considérant notamment la mobilisation du système anti-oxydant dans la réponse cellulaire, pourrait permettre de mieux appréhender l’apport de la mesure du potentiel oxydant dans la compréhension des effets des PM en lien avec le stress oxydant cellulaire

    LES MANIFESTATIONS OSSEUSES REVELATRICES DES LYMPHOMES NON-HODGKINIENS (A PROPOS D'UN CAS CLINIQUE ; REVUE DE LA LITTERATURE)

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    PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
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