OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.
METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.
RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
METHODS: A total of 127 adults aged 18-40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure <120/80mm Hg (n = 59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views.
RESULTS: Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response ( β = .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure.
CONCLUSION: Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.
METHODS: This is a retrospective study over 8-year duration in which all the breast FNABs performed in our institution were recategorized in accordance to the IAC Yokohama reporting system. Kappa coefficient was used to evaluate the agreement between the proposed cytological category and corresponding histological diagnosis, with the level of significance set at 5%. Cyto-histopathological correlation and its diagnostic performance were also assessed.
RESULTS: A total of 1136 breast FNABs were analyzed, including 31 repeat FNABs. Of these, 521 (47.1%) cases had matched histopathological results. Respective ROM for each category was: "insufficient" 13.6%, "benign" 0.4%, "atypical" 25.0%, "suspicious" 85.7%, and "malignant" 100%. There was substantial agreement (κ=0.757) between cytology and histopathological results. Our data revealed a high-diagnostic specificity, sensitivity, positive and negative predictive value of 99.3% (95% CI: 97.6%-99.9%), 94.2% (95% CI: 87.9%-97.9%), 98.0% (95% CI: 92.5%-99.5%), 98.0% (95% CI: 96.1%-99.1%) respectively when both the "suspicious" and "malignant" cases were considered as positive tests, with area under the curve of 0.993.
CONCLUSIONS: The IAC Yokohama system is a reliable, evidence-based, and standardized reporting system that helps to facilitate communication among cytopathologists, radiologists, and surgeons toward individualized patient management.
METHODS: We screened the in-house built fluorescent library compounds that specifically bind human iPS cells. After tertiary screening, the selected probe was analyzed for its ability to detect reprogramming cells in the time-dependent manner using high-content imaging analysis. The probe was compared with conventional dyes in different reprogramming methods, cell types, and cell culture conditions. Cell sorting was performed with the fluorescent probe to analyze the early reprogramming cells for their pluripotent characteristics and genome-wide gene expression signatures by RNA-seq. Finally, the candidate reprogramming factor identified was investigated for its ability to modulate reprogramming efficiency.
RESULTS: We identified a novel BODIPY-derived fluorescent probe, BDL-E5, which detects live human iPS cells at the early reprogramming stage. BDL-E5 can recognize authentic reprogramming cells around 7 days before iPS colonies are formed and stained positive with conventional pluripotent markers. Cell sorting of reprogrammed cells with BDL-E5 allowed generation of an increased number and higher quality of iPS cells. RNA sequencing analysis of BDL-E5-positive versus negative cells revealed early reprogramming patterns of gene expression, which notably included CREB1. Reprogramming efficiency was significantly increased by overexpression of CREB1 and decreased by knockdown of CREB1.
CONCLUSION: Collectively, BDL-E5 offers a valuable tool for delineating the early reprogramming pathway and clinically applicable commercial production of human iPS cells.