Commentary on a combined approach to the problem of developing biomarkers for the prediction of spontaneous preterm labor that leads to preterm birth.

INTRODUCTION: Globally, preterm birth has replaced congenital malformation as the major cause of perinatal mortality and morbidity. The reduced rate of congenital malformation was not achieved through a single biophysical or biochemical marker at a specific gestational age, but rather through a combination of clinical, biophysical and biochemical markers at different gestational ages. Since the aetiology of spontaneous preterm birth is also multifactorial, it is unlikely that a single biomarker test, at a specific gestational age will emerge as the definitive predictive test. METHODS: The Biomarkers Group of PREBIC, comprising clinicians, basic scientists and other experts in the field, with a particular interest in preterm birth have produced this commentary with short, medium and long-term aims: i) to alert clinicians to the advances that are being made in the prediction of spontaneous preterm birth; ii) to encourage clinicians and scientists to continue their efforts in this field, and not to be disheartened or nihilistic because of a perceived lack of progress and iii) to enable development of novel interventions that can reduce the mortality and morbidity associated with preterm birth. RESULTS: Using language that we hope is clear to practising clinicians, we have identified 11 Sections in which there exists the potential, feasibility and capability of technologies for candidate biomarkers in the prediction of spontaneous preterm birth and how current limitations to this research might be circumvented. DISCUSSION: The combination of biophysical, biochemical, immunological, microbiological, fetal cell, exosomal, or cell free RNA at different gestational ages, integrated as part of a multivariable predictor model may be necessary to advance our attempts to predict sPTL and PTB. This will require systems biological data using "omics" data and artificial intelligence/machine learning to manage the data appropriately. The ultimate goal is to reduce the mortality and morbidity associated with preterm birth.

Minimally invasive coronary revascularization in women: A safe approach for a high-risk group.

PURPOSE: Female gender has been shown to be an independent risk factor for mortality in coronary artery bypass graft (CABG) surgery. This report analyzes our early outcomes in 304 women who underwent off-pump coronary artery bypass (OPCAB) surgery at the Washington Hospital Center (Washington, DC) over the last 3 years to determine whether this is a safe approach for coronary bypass in women. METHODS: A retrospective review of 5528 cases of CABG bypass (on-pump) and 840 cases of OPCAB surgery, from June 1996 to July 1999, was performed. Women accounted for 1527 (27.6%) of the on-pump bypass cases and 304 (36.2%) of the OPCABs. All cases without cardiopulmonary bypass were included, with the majority of the most recent cases being multivessel revascularization. The data for analysis were obtained from our cardiac surgery database and included cases from all surgeons operating at the Washington Hospital Center, although the majority of off-pump cases were performed by only a few of these surgeons. RESULTS: The two groups were similar with respect to urgent cases, redos, and other comorbities including preoperative congestive heart failure, peripheral vascular disease, transient ischemic attack (TIA), cerebral vascular accident, and previous myocardial infarction. The mean age for the two groups was similar, 67 years for the off-pump group and 66 years for the on-pump group. The absolute number of all off-pump cases increased each year (from 175 to a total of 373), representing a corresponding increase in percentage of all coronary artery bypass procedures (from 9% to 16%). Of the total number of patients undergoing CABG, the percentage of women who underwent OPCAB doubled from 3% to 6% over the time period analyzed. The percentage of single-vessel cases in the off-pump group fell from 88% to 41% as multivessel bypasses became more routine However, the percentage of patients aged > 75 years was greater for the off-pump group (30%) than for the on-pump group (24%). Otherwise, the two groups differed only in diabetic disease (36% off-pump compared with 46% on-pump; p = 0.001) and previous transcatheter therapy (38% off-pump compared with 29% on-pump; p = 0.003). Patients who had OPCABs received fewer postoperative transfusions (40%) than the on-pump group (59%; p < 0.001). The off-pump group also had fewer neurological complications in the form of TIAs or strokes (0.3%) compared with the on-pump group (3.5%; p = 0.001). The mortality rate was 2.3% off -pump versus 4.1% on pump but did not reach statistical significance in this study (p =.12). CONCLUSION: Myocardial revascularization in women can be performed safely without cardiopulmonary bypass. In our series, the mortality for women receiving off-pump revascularization was lower than the on-pump cohorts despite an older age and higher incidence of diabetes. Although the absolute mortality rates did not reach statistical significance, we were encouraged that the mortality rate for women operated on without CPB dropped to the mortality rate typically seen in men. We also observed a favorable tendency in the off-pump group for a shorter length of stay and a lower incidences of transient ischemic attacks, strokes, post-op bleeding, and blood transfusions. A larger series of patients with multivariate analysis and/or a prospective trial will need to be analyzed in order to confirm our findings.

Equilibrium and transient kinetic studies of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli. Determination of the sugar binding specificity of the L-arabinose-H+ symporter.

The kinetics of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli have been investigated, using a strain that over-produces the symport protein in the cytoplasmic membrane. Equilibrium binding studies revealed a single set of binding sites (2.9-8.9 nmol/mg protein) with a Kd of 0.7-1.0 microM at 22 degrees C. It proved possible to follow the transient kinetics of cytochalasin B binding by measuring the changes in the fluorescence of the L-arabinose-H+ symporter upon binding the ligand, by stopped-flow fluorescence spectroscopy. The association and dissociation rate constants thus determined were confirmed by rapid filtration measurements, using [3H]cytochalasin B, yielding values of 4.5-6.5 microM-1.s-1 and 4-5 s-1, respectively, consistent with Kd values obtained by measuring equilibrium binding of [3H]cytochalasin B by dialysis at 22 degrees C. Titration of the protein fluorescence with cytochalasin B yielded a similar binding site concentration and Kd value to those obtained in equilibrium binding studies. All the measurements of binding site concentration are consistent with a stoichiometry of 1 mol cytochalasin B binding sites/mol L-arabinose-H+ symport protein. Inhibition of both the rate and equilibrium binding of cytochalasin B by sugars indicated the following order of substrate binding 5-thio-D-glucose > D-fucose > L-arabinose > 6-deoxy-6-fluoro-D-galactose > D-xylose approximately 6-deoxy-D-glucose > D-galactose > D-glucose > D-ribose. Neither D-arabinose nor L-fucose had any significant inhibitory effect upon cytochalasin B binding.

A Ca2+-stimulated ATPase activity in rabbit neutrophil membranes.

An ATPase activity specifically stimulated by micromolar Ca2+ concentrations has been identified in association with rabbit neurophil membranes. These studies provide the basis of further characterization of the Ca2+-ATPase activity with regard to neutrophil function.