19 research outputs found
Shotgun next-generation sequencing of maternal plasma: a method for prenatal aneuploidy identification
PURPOSE: Every year, thousands of Americans pursue prenatal diagnosis of fetal aneuploidy though chorionic villus sampling (CVS) or amniocentesis. Because these procedures are invasive and carry an inherent risk for pregnancy loss, they are selectively offered to women who have an increased risk to have a child with a chromosome condition, such as aneuploidy. In order to identify pregnancies at an increased risk, several non-invasive screening methods have been developed. Although quite useful, these screening methods have limited accuracy and can only be completed during specific gestational age windows. Recent discovery of cell free fetal DNA in maternal circulation has created new and exciting possibilities for prenatal screening and non-invasive prenatal diagnosis. This research study explores shotgun next-generation sequencing of fetal DNA in maternal plasma as a method for non-invasive identification of fetal aneuploidy.METHODS: We carried out shotgun next-generation sequencing on samples of maternal plasma DNA obtained in the first trimester of pregnancies with confirmed aneuploidy and control pregnancies. Three Trisomy 21 samples were compared to four control samples in order to identify any differences in the amount of chromosomal material. RESULTS: We identified a statistically significant increase in chromosome 21 material in the cases of Trisomy 21 as compared to the control cases.IMPLICATIONS: This research demonstrates that shotgun next-generation sequencing of maternal plasma DNA can successfully identify Trisomy 21, showing that it is possible to detect fetal aneuploidy using this noninvasive method. This technology could potentially be used as a method of noninvasive screening for fetal aneuploidy, which is likely to have improved accuracy over other screening methods. Development of a screening test with greater sensitivity and specificity could have significant public health implications. This would not only provide more accurate identification of pregnancies at an increased risk for aneuploidy, but it would also reduce the number of false positives. This in turn would reduce the number of pregnancies that are unnecessarily classified as "high risk", preventing avoidable parental anxiety and reducing the number of pregnancies that are put at unnecessary risk of invasive prenatal diagnostic procedures
Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice
Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1ÎČ, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress. © 2012 Brass et al
Postpartum-specific anxiety as a predictor of infant-feeding outcomes and perceptions of infant-feeding behaviours: new evidence for childbearing specific measures of mood
Studies of pregnancy-specific anxiety suggest that it is a distinct construct which predicts perinatal outcomes more effectively than other general measures of anxiety. In response, a novel measure of postpartum-specific anxiety (PSAS) has been developed and validated, but it is not yet clear whether it possesses the same predictive power as its pregnancy-specific counterparts. The aim of this short-term prospective study was to (a) test the predictive validity of the PSAS in the context of one specific perinatal outcome, infant-feeding, and (b) examine whether the PSAS may be more efficacious at predicting infant-feeding outcomes and behaviours than the more commonly used general measures. Eight hundred mothers of infants aged between 0 and 6 months completed the PSAS alongside general measures of anxiety and depression at baseline. A subsample (n = 261) returned to complete a follow-up questionnaire examining infant-feeding outcomes and behaviours two weeks later. Hierarchical regression models revealed that the PSAS was associated with lower odds of breastfeeding exclusively, and breastfeeding in any quantity in the first 6 months postpartum. PSAS scores were also significantly associated with infant-feeding behaviours including a lower perceived enjoyment of food, and greater perceived food responsiveness and satiety responsiveness in the infant. As hypothesised, the PSAS was a stronger predictor of infant-feeding outcomes and behaviours than general anxiety and depression. The findings provide evidence for the predictive validity of the PSAS and call for the use of childbearing specific measures of mood when attempting to predict perinatal outcomes. Replication of these findings across other indices of maternal and infant health is now necessary
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Chemotherapyâinduced thrombocytopenia in pediatric oncology: Scope of the problem and opportunities for intervention
Background
Chemotherapyâinduced thrombocytopenia (CIT) is a known hematologic complication of oncology treatment. This singleâinstitution study examines the degree with which CIT impacts specific pediatric solid tumor cohorts reflected by platelet transfusion burden and treatment modifications.
Procedure
Data regarding clinically relevant CIT were obtained via a retrospective chart review of pediatric solid tumor patients treated at Memorial Sloan Kettering Cancer Center from 2013 to 2020. Patients were stratified based on histologic diagnoses as well as chemotherapy regimen. CIT impact was assessed through platelet transfusion means, chemotherapy dose reductions, and treatment delays.
Results
A total of 150 patients were included with mean age 10.3 [0.2â21.0]. Patients receiving therapy for highârisk neuroblastoma and localized Ewing sarcoma, both of which included highâdose cyclophosphamide and doxorubicin, required the most platelet transfusions over the treatment course, with a mean of 13 and 9, respectively. Reduced relative dose intensity (RDI), due in part to CIT, was greatest for the patients receiving therapy for highârisk and intermediateârisk rhabdomyosarcoma. Fiftyâsix percent of highârisk patients experienced a reduced RDI during the final two cycles of treatment and 69% of intermediateârisk patients experienced one during the final four cycles of treatment.
Conclusions
The impact of CIT varied by the administered chemotherapy regimens and dose intensity of chemotherapy agents. This study demonstrated that CIT causes both marked platelet transfusion burden as well as treatment reduction and delay within certain solid tumor cohorts. This can lend to future studies aimed at reducing the burden of CIT and targeting the most atârisk populations
Retraction: Innate Immune Activation by Inhaled Lipopolysaccharide, Independent of Oxidative Stress, Exacerbates Silica-Induced Pulmonary Fibrosis in Mice.
Retraction: Innate Immune Activation by Inhaled Lipopolysaccharide, Independent of Oxidative Stress, Exacerbates Silica-Induced Pulmonary Fibrosis in Mice
Gender influences the response to experimental silica-induced lung fibrosis in mice
Accumulating evidence suggests that gender can have a profound effect on incidence and severity of a variety of pulmonary diseases. To address the influence of gender on the development of silica-induced pulmonary fibrosis, we instilled 0.2 g/kg silica into male and female C57BL/6 mice and examined the fibrotic and inflammatory response at 14 days postexposure. Both silica-exposed male and female mice had significant increases in total lung hydroxyproline compared with saline controls. However, silica-exposed female mice had significantly less total lung hydroxyproline than silica-exposed male mice. This observation was confirmed by color thresholding image analysis. Interestingly, silica-exposed female mice had significantly more inflammatory cells, the majority of which were macrophages, as well as higher levels of the macrophage-specific chemokines MCP-1 and CCL9 in whole lung lavage compared with silica-exposed male mice. We also show that at baseline, estrogen receptor α (ERα) mRNA expression is lower in female mice than in males and that ERα mRNA expression is decreased by silica exposure. Finally, we show that the response of ovariectomized female mice to silica instillation is similar to that of male mice. These observations together show that gender influences the lung response to silica
Histology immediately after the end of inhalation challenge.
<p>(A) Saline-Saline; (B) Silica-Saline; (C) Saline-LPS; and (D) Silica-LPS exposed mice immediately after the end of either saline or LPS inhalation challenge. nâ=â6/group. Images were taken in anatomically comparable regions of the lung at 5Ă (main images) or 20Ă (Inset in panel D) magnification. Barâ=â100 microns.</p
Whole lung lavage immediately after the end of inhalation challenge in mice treated with drinking water alone or drinking water supplemented with 2 mg/ml NAC during LPS exposure.
<p>(A) Total cellsĂ10<sup>5</sup>; (B) total macrophagesĂ10<sup>5</sup>; (C) total neutrophilsĂ10<sup>5</sup>; and (D) total lymphocytesĂ10<sup>5</sup>. Data are presented as Mean + SEM. nâ=â8/group. * p<0.05 LPS vs. Saline (significant difference due to inhalation challenge); <sup>â§</sup> p<0.05 vs. regular drinking water (significant difference due to NAC treatment alone); # p<0.05 Silica vs. Saline (significant difference due to silica instillation or combined Silica and LPS).</p
Whole lung cytokines immediately after and 21 days after the end of inhalation challenge.
<p>Total (A) MCP-1; (B) MIP-2; (C) KC; and (D) IL-1ÎČ in whole lung lavage. Data are presented as Mean + SEM and are representative of two such experiments. nâ=â6/group. * p<0.05 LPS vs. Saline (significant difference due to inhalation challenge); # p<0.05 Silica vs. Saline (significant difference due to silica instillation or combined Silica and LPS).</p