Reduced incidence of early preterm birth in the State of Thuringia following an intravaginal pH-self-monitoring screening program.

BACKGROUND: Effective prevention of preterm birth as cause of serious risks for the infant as well as the mother pre- and postpartum is one of the still unsolved problems in modern medicine. METHOD: The government of the State of Thuringia in cooperation with the professional organization of obstetricians and gynecologists decided in 2016 to reestablish and promote a self-care screening program based on intravaginal (i.vag.) pH measurement to reduce the incidence of preterm birth by early diagnosis and therapy of genital infection. RESULTS: Starting at zero in 2016, > 80% of pregnant women in the state had their vaginal pH monitored at the end of 2018 (n = 17.180). This was associated with a reduced incidence of early preterm birth measured by gestational week ≤ 32 (1.46 vs. 1.26%). CONCLUSION: The fourth millennium goal missed worldwide in 2015 as well as the newly declared third objective of the UN could come closer using the simple and cheap i.vag. pH-self-screening regime in prevention of preterm birth, an approach partly turning the woman from being object of medical care to being the subject in self-control of her pregnancy. This is also a well perceived change in paradigm from the perspective of females as well as physicians.

Island Ripening via a Polymerization-Depolymerization Mechanism.

In catalytic methanol oxidation on ultrathin vanadium oxide layers on Rh(111) (Θ_{V}≈0.2 monolayer equivalent) we observe a 2D ripening of the VO_{x} islands that is controlled by the catalytic reaction. Neighboring VO_{x} islands move under reaction conditions towards each other and coalesce. The motion and the coalescence of the islands are explained by a polymerization-depolymerization equilibrium that is sensitive to gradients in the adsorbate coverages.

Accuracy to 2nd International HIV-1 RNA WHO Standard: assessment of three generations of quantitative HIV-1 RNA nucleic acid amplification tests.

BACKGROUND: Standardization of quantitative HIV-1 tests to a global primary standard is required by regulatory authorities to ensure comparability of test results across different assays and platforms of different manufacturers. OBJECTIVES AND STUDY DESIGN: Three generations of quantitative HIV-1 tests, the COBAS(®) AMPLICOR(®) HIV-1 Monitor Test, v1.5 (HIV-1 Monitor test v1.5); the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test (HIV-1 TaqMan(®) test v1.0); and the dual-target-based COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test, v2.0 (HIV-1 TaqMan(®) test v2.0), were assessed for accuracy to World Health Organization (WHO) 2nd International Standard for human immunodeficiency virus 1 (HIV-1) RNA (NIBSC code 97/650) at concentration levels below 1667 IU/mL including relevant medical decision points. RESULTS: With the 2nd WHO Standard the mean difference across all concentrations was -0.07 log(10) for the HIV-1 Monitor test v1.5; +0.12 log(10) for the HIV-1 TaqMan(®) test v1.0; and +0.09 log(10) for the HIV-1 TaqMan(®) test v2.0. Linearity, including concentrations below the claimed limit of quantitation, was demonstrated for HIV-1 TaqMan(®) test v2.0. The HIV-1 TaqMan(®) test v1.0 showed a trend towards higher quantitation at very low concentration levels and the HIV-1 Monitor test v1.5 had a tendency towards lower quantitation at low concentration levels. CONCLUSIONS: All three assays are closely traceable to the primary WHO HIV-1 RNA standard for in vitro diagnostic IVD assays. Compared to the other two assays, the HIV-1 TaqMan(®) test v2.0 showed better linearity around the limit of detection and below.

Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach.

BACKGROUND: HIV-1 RNA viral load is a key parameter for reliable treatment monitoring of HIV-1 infection. Accurate HIV-1 RNA quantitation can be impaired by primer and probe sequence polymorphisms as a result of tremendous genetic diversity and ongoing evolution of HIV-1. A novel dual HIV-1 target amplification approach was realized in the quantitative COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 (HIV-1 TaqMan test v2.0) to cope with the high genetic diversity of the virus. OBJECTIVES AND STUDY DESIGN: The performance of the new assay was evaluated for sensitivity, dynamic range, precision, subtype inclusivity, diagnostic and analytical specificity, interfering substances, and correlation with the COBAS AmpliPrep/COBAS TaqMan HIV-1 (HIV-1 TaqMan test v1.0) predecessor test in patients specimens. RESULTS: The new assay demonstrated a sensitivity of 20 copies/mL, a linear measuring range of 20-10,000,000 copies/mL, with a lower limit of quantitation of 20 copies/mL. HIV-1 Group M subtypes and HIV-1 Group O were quantified within +/-0.3 log(10) of the assigned titers. Specificity was 100% in 660 tested specimens, no cross reactivity was found for 15 pathogens nor any interference for endogenous substances or 29 drugs. Good comparability with the predecessor assay was demonstrated in 82 positive patient samples. In selected clinical samples 35/66 specimens were found underquantitated in the predecessor assay; all were quantitated correctly in the new assay. CONCLUSIONS: The dual-target approach for the HIV-1 TaqMan test v2.0 enables superior HIV-1 Group M subtype coverage including HIV-1 Group O detection. Correct quantitation of specimens underquantitated in the HIV-1 TaqMan test v1.0 test was demonstrated.

Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation.

Few cases of de novo unbalanced X;autosome translocations associated with a normal or mild dysmorphic phenotype have been described. We report a 3-year-old dizygotic female twin with prenatally ascertained increased nuchal translucency. Prenatal chromosome studies revealed nearly complete trisomy 15 due to a de novo unbalanced translocation t(X;15)(q22;q11.2) confirmed postnatally. A mild phenotype was observed with normal birth measurements, minor facial dysmorphic features (hypertelorism, short broad nose, and a relatively long philtrum), and moderate developmental delay at the age of 3 years in comparison to her male fraternal twin. Replication timing utilizing BrdU and acridine-orange staining showed that the der(X) chromosome was late-replicating with variable spreading of inactivation into the translocated 15q segment. The der(X) was determined to be of paternal origin by analyses of polymorphic markers and CGG-repeat at FMR1. Methylation analysis at the SNRPN locus and analysis of microsatellites on 15q revealed paternal isodisomy with double dosage for all markers and the unmethylated SNRPN gene. The Xq breakpoint was mapped within two overlapping BAC clones RP11-575K24 and RP13-483F6 at Xq22.3 and the 15q breakpoint to 15q11.2, within overlapping clones RP11-509A17 and RP11-382A4 that are all significantly enriched for LINE-1 elements (36.6%, 43.0%, 26.6%, 22.0%, respectively). We speculate that the attenuated phenotype may be due to inactivation spreading into 15q, potentially facilitated by the enrichment of LINE-1 elements at the breakpoints. In silico analysis of breakpoint regions revealed the presence of highly identical low-copy repeats (LCRs) at both breakpoints, potentially involved in generating the translocation.