Low-dose betamethasone-acetate for fetal lung maturation in preterm sheep

BackgroundAntenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.ObjectiveThe purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.Study designGroups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.ResultsAll betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance, gas exchange, and ventilation efficiency similarly to the standard treatment of 2 doses of 0.25 m/kg of betamethasone-acetate+betamethasone-phosphate. Betamethasone-acetate 0.125 mg/kg resulted in lower maternal and fetal peak plasma concentrations and decreased fetal exposure to betamethasone compared with betamethasone-phosphate 0.125 mg/kg.ConclusionA single dose of betamethasone-acetate results in similar fetal lung maturation as the 2-dose clinical formulation of betamethasone-phosphate+betamethasone-acetate with decreased fetal exposure to betamethasone. A lower dose of betamethasone-acetate may be an effective alternative to induce fetal lung maturation with less risk to the fetus

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Internal medicine specialists' attitudes towards working part-time: a comparison between 1996 and 2004

BACKGROUND: Although medical specialists traditionally hold negative views towards working part-time, the practice of medicine has evolved. Given the trend towards more part-time work and that there is no evidence that it compromises the quality of care, attitudes towards part-time work may have changed as well in recent years. The aim of this paper was to examine the possible changes in attitudes towards part-time work among specialists in internal medicine between 1996 and 2004. Moreover, we wanted to determine whether these attitudes were associated with individual characteristics (age, gender, investments in work) and whether attitudes of specialists within a partnership showed more resemblance than specialists' attitudes from different partnerships. METHODS: Two samples were used in this study: data of a survey conducted in 1996 and in 2004. After selecting internal medicine specialists working in general hospitals in The Netherlands, the sample consisted of 219 specialists in 1996 and 363 specialists in 2004. They were sent a questionnaire, including topics on the attitudes towards part-time work. RESULTS: Internal medicine specialists' attitudes towards working part-time became slightly more positive between 1996 and 2004. Full-time working specialists in 2004 still expressed concerns regarding the investments of part-timers in overhead tasks, the flexibility of task division, efficiency, communication and continuity of care. In 1996 gender was the only predictor of the attitude, in 2004 being a full- or a part-timer, age and the time invested in work were associated with this attitude. Furthermore, specialists' attitudes were not found to cluster much within partnerships. CONCLUSION: In spite of the increasing number of specialists working or preferring to work part-time, part-time practice among internal medicine specialists seems not to be fully accepted. The results indicate that the attitudes are no longer gender based, but are associated with age and work aspects such as the number of hours worked. Though there is little evidence to support them, negative ideas about the consequences of part-time work for the quality of care still exist. Policy should be aimed at removing the organisational difficulties related to part-time work and create a system in which part-time practice is fully integrated and accepted

Ion beam synthesis of cubic FeSi2

Cubic FeSi, precipitates were synthesized in Si ( 100) by room-temperature Fe ion implantation followed by Si 500 keV ion beam induced epitaxial crystallization at 320 “C!. High resolution electron microscopy and Rutherford backscattering/channeling techniques show that the cubic precipitates occur in both aligned (A) and twinned (B) types with a lattice parameter very similar to that of the Si (100) matrix

Low-temperature ion-induced epitaxial growth of alfa-FeSi2 and cubic FeSi2 in Si

Ion-beam-induced epitaxial crystallization of amorphous Si implanted with Fe to 18 at. % peak concentration was studied. The structure of the specimen was characterized using transmission electron microscopy and Rutherford backscattering spectrometry. Both cubic FeSi, and a-FeSi, were formed in epitaxy with the Si matrix with two types of orientations (fully aligned and twinned). The twins of a-FeSi, and those of cubic FeSi, were found to have exactly the same type of epitaxial relationship as for the aligned ones. The thermodynamically stable /3-FeS& is not formed, demonstrating that ion-beam-induced crystallization can lead to preferential phase formation as well as to epitaxy

Ion beam synthesis of cubic FeSi2

Cubic FeSi, precipitates were synthesized in Si ( 100) by room-temperature Fe ion implantation followed by Si 500 keV ion beam induced epitaxial crystallization at 320 “C!. High resolution electron microscopy and Rutherford backscattering/channeling techniques show that the cubic precipitates occur in both aligned (A) and twinned (B) types with a lattice parameter very similar to that of the Si (100) matrix