Objectives To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, ...and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions.Design First phase of a semifactorial randomised controlled trial.Setting Nine consultant led maternity units, United Kingdom.Participants 125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks’ gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management.Interventions Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks’ gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks’ gestation).Main outcome measures The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates.Results Ursodeoxycholic acid reduced itching by −16 mm (95% confidence interval −27 mm to −6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval −3 to 34); this would represent a number needed to treat of 6, but it failed to reach significance. Early term delivery did not increase caesarean sections (7/30 (23%) in the early term delivery group versus 11/32 (33%) in the expectant management group (relative risk 0.70, 95% confidence interval 0.31 to 1.57). No serious harms were noted in either trial. 22% (73/325) of eligible women participated in the drug trial and 19% (39/209) in the timing of delivery trial; both groups had a similar spectrum of disease severity to non-participants.Conclusions Ursodeoxycholic acid significantly reduces pruritus, but the size of the benefit may be too small for most doctors to recommend it, or for most women to want to take it. Women are, however, likely to differ in whether they consider the benefit to be worthwhile. Planned early term delivery seems not to increase incidence of caesarean section, although a small increase cannot be excluded. A trial to test whether ursodeoxycholic acid reduces adverse perinatal outcomes would have to be large, but is feasible. A trial to test the effect of early term delivery on adverse fetal outcomes would have to be significantly larger and may not be feasible.Trial registration Current Controlled Trials ISRCTN37730443.
The claim of a dramatic reduction in hot flushes fails to mention that symptoms recur when hormone replacement therapy (HRT) is stopped and that the largest trial (Women's Health Initiative) showed ...no benefit on quality of life. 1 The graphs seem to have been derived from, and give equal weight to, the largest randomised trial and the largest observational study. (16 February.) 2 Gabriel Sanchez R, Sanchez Gomez LM, Carmona L, Roqué i Figuls M, Bonfill Cosp X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women.
Excess electrons facilitate redox reactions at the technologically relevant anatase TiO
2
(101) surface. The availability of these electrons is related to the defect concentration at the surface. We ...present two-photon (2PPE, 3.10–3.54 eV) and ultraviolet (UPS, 21.2 & 40.8 eV) photoemission spectroscopy measurements evidencing an increased concentration of excess electrons following electron bombardment at room temperature. Irradiation-induced surface oxygen vacancies are known to migrate into the sub-surface at this temperature, quickly equilibrating the surface defect concentration. Hence, we propose that the irradiated surface is hydroxylated. Peaks in UPS difference spectra are observed centred 8.45, 6.50 and 0.73 eV below the Fermi level, which are associated with the 3σ and 1π hydroxyl molecular orbitals and Ti 3d band gap states, respectively. The higher concentration of excess electrons at the hydroxylated anatase (101) surface may increase the potential for redox reactions.
Geometric structure of TiO2(011)(2 x 1) Torrelles, X; Cabailh, G; Lindsay, R ...
Physical review letters,
10/2008, Letnik:
101, Številka:
18
Journal Article
Recenzirano
Surface x-ray diffraction has been employed to elucidate the surface structure of the (011)-(2 x 1) termination of rutile TiO2. The data are inconsistent with previously proposed structures. Instead, ...an entirely unanticipated geometry emerges from the structure determination, which is terminated by zigzag rows of twofold coordinated oxygen atoms asymmetrically bonded to fivefold titanium atoms. The energetic stability of this structure is demonstrated by ab initio total energy calculations.
The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident ...bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.
Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy and presents with maternal pruritus, raised concentrations of serum bile acids and abnormal liver ...function tests. ICP is associated with increased rates of spontaneous and iatrogenic preterm labour, fetal hypoxia, meconium-stained amniotic fluid and intrauterine death. Some clinicians treat ICP with ursodeoxycholic acid (UDCA) to improve maternal pruritus and biochemical abnormalities. However, there are currently no data to support the use of UDCA to improve pregnancy outcome as none of the trials performed to date have been powered to address this question.
The PITCHES trial is a triple-masked, placebo-controlled randomised trial, to evaluate UDCA versus placebo in women with ICP between 20 + 0 to 40 + 6 weeks' gestation. The primary objective of the trial is to determine if UDCA treatment of women with ICP between 20 + 0 and 40 + 6 weeks' gestation reduces the primary perinatal outcome: a composite of perinatal death (as defined by in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (less than 37 weeks' gestation) or neonatal unit admission for at least 4 h (from infant delivery until hospital discharge). The secondary objectives of the trial are (1) to investigate the effect of UDCA on other short-term outcomes for both mother and infant and (2) to assess the impact of UDCA on health care resource use, in terms of the total number of nights for mother and infant, together with level of care.
Current practice in the UK at the time of trial commencement for the treatment of ICP is inconsistent, with some units routinely prescribing UDCA, others prescribing very little and the remainder offering it variably. Our previous pilot trial of UDCA in women with ICP demonstrated that the trial would be feasible, and the research question remains active and unanswered. Results are highly likely to influence clinical practice, through direct management and impact on national and international guidelines.
ISRCTN registry, ID: ISRCTN91918806 . Prospectively registered on 27 August 2015.
Controlled dual mode scanning tunneling microscopy (STM) experiments and first-principles simulations show that the tunneling conditions can significantly alter the positive-bias topographic contrast ...of geometrically corrugated titania surfaces such as rutile TiO2(011)-(2×1). Depending on the tip-surface distance, two different contrasts can be reversibly imaged. STM simulations which either include or neglect the tip-electronic structure, carried out at three density functional theory levels of increasing accuracy, allow assignment of both contrasts on the basis of the TiO2(011)-(2×1) structure proposed by Torrelles et al. Phys. Rev. Lett. 101, 185501 (2008). Finally, the mechanisms of contrast formation are elucidated in terms of the subtle balance between the surface geometry and the different vacuum decay lengths of the topmost Ti(3d) and O(2p) states probed by the STM-tip apex.
Forty percent of babies who are stillborn born die after 36 weeks gestation and have no lethal structural abnormality. Maternal perception of reduced fetal movement (RFM) is associated with ...stillbirth and is related to abnormal placental structure and function. The ultimate objective of this trial is to assess whether for women with RFM, intervention directed by measurement of placental biochemical factors in addition to standard care improves pregnancy outcome compared with standard care alone. This is the protocol for a pilot trial to determine the feasibility of a definitive trial and also provide proof of concept that informing care by measurement of placental factors improves neonatal outcomes.
ReMIT-2 is a multicentre, pilot randomised controlled trial of care informed by results of an additional placental factor blood test versus standard care alone for women presenting with RFM at or after 36
weeks gestation. Participants will be randomised 1:1 to the intervention arm where the blood test result is revealed and acted on, or to the control arm where the blood sample is not tested immediately and therefore the result cannot be acted on. All participants will be followed up six weeks after delivery to assess their health status and views of the trial, along with healthcare costs. A sub-group will be interviewed within 16 weeks after delivery to further explore their views of the trial. Outcomes to determine feasibility of a definitive trial include number of potentially eligible women, proportion lost to follow-up, clinical characteristics at randomisation, reasons for non-recruitment, compliance with the trial intervention and views of participants and clinicians about the trial. Proof of concept outcomes include: rates of induction of labour; Caesarean birth; and a composite neonatal outcome of stillbirths and deaths before discharge, 5-min Apgar score < 7, umbilical artery pH < 7.05 and admission to neonatal unit for > 48 h.
Results from this pilot trial will help determine whether a large definitive trial is feasible. Such a study would provide evidence to guide management of women with RFM and reduce stillbirths.
ISRCTN Registry, ISRCTN12067514 . Registered on 8 September 2017.
The Mars Odyssey Gamma-Ray Spectrometer is a suite of three different instruments, a gamma subsystem (GS), a neutron spectrometer, and a high-energy neutron detector, working together to collect data ...that will permit the mapping of elemental concentrations on the surface of Mars. The instruments are complimentary in that the neutron instruments have greater sensitivity to low amounts of hydrogen, but their signals saturate as the hydrogen content gets high. The hydrogen signal in the GS, on the other hand, does not saturate at high hydrogen contents and is sensitive to small differences in hydrogen content even when hydrogen is very abundant. The hydrogen signal in the neutron instruments and the GS have a different dependence on depth, and thus by combining both data sets we can infer not only the amount of hydrogen, but constrain its distribution with depth. In addition to hydrogen, the GS determines the abundances of several other elements. The instruments, the basis of the technique, and the data processing requirements are described as are some expected applications of the data to scientific problems.
Metastasis to local lymph nodes via the lymphatic vessels is a common step in the spread of solid tumors. To investigate the molecular mechanisms underlying the spread of cancer by the lymphatics, we ...examined the ability of vascular endothelial growth factor (VEGF)-D, a ligand for the lymphatic growth factor receptor VEGFR-3/Flt-4, to induce formation of lymphatics in a mouse tumor model. Staining with markers specific for lymphatic endothelium demonstrated that VEGF-D induced the formation of lymphatics within tumors. Moreover, expression of VEGF-D in tumor cells led to spread of the tumor to lymph nodes, whereas expression of VEGF, an angiogenic growth factor which activates VEGFR-2 but not VEGFR-3, did not. VEGF-D also promoted tumor angiogenesis and growth. Lymphatic spread induced by VEGF-D could be blocked with an antibody specific for VEGF-D. This study demonstrates that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread.
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