Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.

Chronic obstructive pulmonary disease (COPD) is a major health burden in adults and cigarette smoking is considered the most important environmental risk factor of COPD. Chromosome 15q25.1 locus is associated with both COPD and smoking. Our study aims at understanding the mechanism underlying the association of chromosome 15q25.1 with COPD through epigenetic and transcriptional variation in a population-based setting. To assess if COPD-associated variants in 15q25.1 are methylation quantitative trait loci, epigenome-wide association analysis of four genetic variants, previously associated with COPD (P < 5 × 10-8) in the 15q25.1 locus (rs12914385:C>T-CHRNA3, rs8034191:T>C-HYKK, rs13180:C>T-IREB2 and rs8042238:C>T-IREB2), was performed in the Rotterdam study (n = 1489). All four variants were significantly associated (P < 1.4 × 10-6) with blood DNA methylation of IREB2, CHRNA3 and PSMA4, of which two, including IREB2 and PSMA4, were also differentially methylated in COPD cases and controls (P < 0.04). Further additive and multiplicative effects of smoking were evaluated and no significant effect was observed. To evaluate if these four genetic variants are expression quantitative trait loci, transcriptome-wide association analysis was performed in 1087 lung samples. All four variants were also significantly associated with differential expression of the IREB2 3'UTR in lung tissues (P < 5.4 × 10-95). We conclude that regulatory mechanisms affecting the expression of IREB2 gene, such as DNA methylation, may explain the association between genetic variants in chromosome 15q25.1 and COPD, largely independent of smoking.

Prenatal identification of invasive placentation using magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVE: To assess systematically the performance of prenatal magnetic resonance imaging (MRI) in diagnosing the presence, degree and topography of disorders of invasive placentation and to explore the role of the different MRI signs in predicting these disorders. The diagnostic accuracy of ultrasound and MRI in the detection of invasive placentation was also compared. METHODS: MEDLINE, EMBASE, CINAHL and The Cochrane Library, including The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and The Cochrane Central Register of Controlled Trials, were searched electronically utilizing combinations of the relevant medical subject heading terms, keywords and word variants for 'invasive placentation' and 'magnetic resonance imaging'. Only prospective studies reporting a diagnosis of invasive placentation at the time of MRI and retrospective studies in which the radiologist was blinded to the final results were included in the analysis. The MRI signs explored were: uterine bulging, heterogeneous signal intensity, dark intraplacental bands on T2 weighted sequences, focal interruption of the myometrium and tenting of the bladder. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-) and diagnostic odds ratio (DOR) were based, depending on the number of studies, upon DerSimonian-Laird random-effect or hierarchical summary receiver-operating characteristics models. RESULTS: A total of 18 studies involving 1010 pregnancies at risk for invasive placentation were included. The overall diagnostic accuracy of MRI in detecting the presence of invasive placentation was: sensitivity, 94.4% (95% CI, 86.0-97.9%); specificity, 84.0% (95% CI, 76.0-89.8%); LR+, 5.91 (95% CI, 3.73-9.39); LR-, 0.07 (95% CI, 0.02-0.18); DOR, 89.0 (95% CI, 22.8-348.1). MRI had a high predictive accuracy in assessing both the depth and topography of placental invasion. All five MRI signs showed good predictive accuracy in the diagnosis of disorders of invasive placentation. There was no difference in either the sensitivity (P = 0.24) or the specificity (P = 0.91) between ultrasound and MRI for the detection of invasive placentation. CONCLUSIONS: Prenatal MRI is highly accurate in diagnosing disorders of invasive placentation. Ultrasound and MRI have comparable predictive accuracy. Large population-based studies are needed in order to assess whether ultrasound can predict the depth and topography of placental invasion as reliably as can MRI.

Ureasil-polyether hybrid film-forming materials.

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules.

Persistent leukocyturia and loss of renal function in a prospectively monitored cohort of HIV-infected patients treated with indinavir.

Symptomatic nephrotoxicity is a well-known complication of indinavir treatment. However, little is known about the relevance of other abnormalities, such as leukocyturia during use of indinavir. We determined the prevalence, risk factors, and consequences of persistent leukocyturia in a prospectively monitored cohort of indinavir users in three adult outpatient clinics. Patients were monitored for nephrotoxicity at regular visits (every 3 months) between August 1998 and September 2000. Monitoring involved urine dipstick analysis and microscopy for pH, erythrocytes, leukocytes, and indinavir crystals. The urine albumin concentration/creatinine concentration ratio and serum creatinine and indinavir plasma concentrations were measured, and urinary tract infection was excluded. Urologic symptoms were retrieved from medical records. Of 184 patients with at least one assessment, 35% had leukocyturia (i.e., >75 cells/microL) at least once during the study period, which coincided with mild increase in the serum albumin level, erythrocyturia, and crystalluria. Thirty-two (24%) of 134 patients with two or more assessments had persistent leukocyturia (i.e., on two or more occasions). Risk factors were indinavir plasma concentration of >9 mg/L, urine pH of >5.7, and crystalluria. Persistent leukocyturia was associated with a gradual loss of renal function but not with urologic symptoms. The data show that leukocyturia is a frequent finding and emphasize the need for monitoring renal function during indinavir treatment, even in the absence of urologic symptoms.