Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.
Introduction: Amniotic fluid "sludge" has been associated with an increased rate of spontaneous preterm delivery before 35 weeks, a higher frequency of clinical and histologic chorioamnionitis in a high-risk population. Only one study evaluating the use of antibiotics in the presence of amniotic fluid "sludge" showed reduced rates of spontaneous preterm birth at <34 weeks. The objective of this study was to evaluate routine antibiotic treatment in the presence of amniotic fluid "sludge" for prevention of preterm delivery. Material and methods: A historically controlled observational study was performed between October 2010 and January 2015, including a total of 86 pregnant women with singleton pregnancies and the presence of amniotic fluid "sludge" at ultrasound.
To test the effectiveness of cervical pessary in addition to vaginal progesterone for the prevention of preterm birth in women with midpregnancy short cervixes.
METHODS:We performed a multicenter, open-label, randomized controlled trial in 17 perinatal centers. Asymptomatic women with singleton or twin pregnancies and cervical lengths of 30 mm or less, measured at 18 0/7-22 6/7 weeks of gestation, were randomized to cervical pessary plus vaginal progesterone (pessary plus progesterone group) or vaginal progesterone only (progesteroneonly group) (200 mg/day). Treatments were used from randomization to 36 weeks of gestation or delivery. The primary outcome was a composite of neonatal mortality and morbidity. Secondary outcomes were delivery before 37 weeks and before 34 weeks of gestation. Analysis was performed according to intention to treat.
Two intramolecularly quenched fluorogenic peptides containing oaminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (EDDnp) groups at amino-and carboxyl-terminal amino acid residues, AbzDArg-Arg-Leu-EDDnp (Abz-DRRL-EDDnp) and Abz-DArg-Arg-PheEDDnp (Abz-DRRF-EDDnp), were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-DRRL-EDDnp and Abz-DRRFEDDnp were K m = 2.8 µM, k cat = 5.3 min -1 , k cat /K m = 2 min -1 µM -1 and K m = 5.0 µM, k cat = 7.0 min -1 , k cat /K m = 1.4 min -1 µM -1 , respectively. The high specificity of these substrates was demonstrated by their resistance to hydrolysis by metalloproteases [thermolysin (EC 3.4.24.2), angiotensin-converting enzyme (ACE; EC 3.4.24.15)], serineproteases [trypsin (EC 3.4.21.4), α-chymotrypsin (EC 3.4.21.1)] and proteases present in tissue homogenates from kidney, lung, brain and testis. The blocked amino-and carboxyl-terminal amino acids protected these substrates against the action of aminopeptidases, carboxypeptidases and ACE. Furthermore, DR amino acids ensured total protection of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp against the action of thermolysin and trypsin. Leu-EDDnp and Phe-EDDnp were resistant to hydrolysis by α-chymotrypsin. The high specifity of these substrates suggests their use for specific NEP assays in crude enzyme preparations.
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