CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic.

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.

Porous and strong three-dimensional carbon nanotube coated ceramic scaffolds for tissue engineering.

Biomaterials research is investigating increasingly complex materials capable of mirroring the highly organized biochemical and architectural environments of the body. Accordingly, tissue scaffolds with nanoscale properties that mirror the fibrous proteins present in tissue are being developed. Such materials can benefit from the inherent dimensional similarities and nanocomposite nature of the cellular environment, altering nanoscale dimensional and biochemical properties to mimic the regulatory characteristics of natural cellular environments. One nanomaterial which demonstrates potential across a diverse range of biomaterial applications is carbon nanotubes (CNTs). Building on previous reports, a method to coat CNTs throughout 3D porous structures is developed. Through modifications to typical chemical vapour deposition (CVD), a high-quality uniform coating of carbon nanotubes (CNTs) is demonstrated over ß-tricalcium phosphate/hydroxyapatite (or TCP/HA), which is in clinical use; and the high-mechanical-strength multicomponent ceramic Ca2ZnSi2O7-ZnAl2O4, (or Sr-HT-Gah). The resulting materials address deficiencies of previously reported CNT biomaterials by simultaneously presenting properties of high porosity, biocompatibility and a mechanical stability. Together, this unique combination of properties makes these scaffolds versatile materials for tissue engineering in load bearing applications.

Effects of continuity of care by a primary midwife (caseload midwifery) on caesarean section rates in women of low obstetric risk: the COSMOS randomised controlled trial.

OBJECTIVE: To determine whether primary midwife care (caseload midwifery) decreases the caesarean section rate compared with standard maternity care. DESIGN: Randomised controlled trial. SETTING: Tertiary-care women's hospital in Melbourne, Australia. POPULATION: A total of 2314 low-risk pregnant women. METHODS: Women randomised to caseload received antenatal, intrapartum and postpartum care from a primary midwife with some care by 'back-up' midwives. Women randomised to standard care received either midwifery or obstetric-trainee care with varying levels of continuity, or community-based general practitioner care. PRIMARY OUTCOME: caesarean birth. Secondary outcomes included instrumental vaginal births, analgesia, perineal trauma, induction of labour, infant admission to special/neonatal intensive care, gestational age, Apgar scores and birthweight. RESULTS: In total 2314 women were randomised-1156 to caseload and 1158 to standard care. Women allocated to caseload were less likely to have a caesarean section (19.4% versus 24.9%; risk ratio [RR] 0.78; 95% CI 0.67-0.91; P = 0.001); more likely to have a spontaneous vaginal birth (63.0% versus 55.7%; RR 1.13; 95% CI 1.06-1.21; P < 0.001); less likely to have epidural analgesia (30.5% versus 34.6%; RR 0.88; 95% CI 0.79-0.996; P = 0.04) and less likely to have an episiotomy (23.1% versus 29.4%; RR 0.79; 95% CI 0.67-0.92; P = 0.003). Infants of women allocated to caseload were less likely to be admitted to special or neonatal intensive care (4.0% versus 6.4%; RR 0.63; 95% CI 0.44-0.90; P = 0.01). No infant outcomes favoured standard care. CONCLUSION: In settings with a relatively high baseline caesarean section rate, caseload midwifery for women at low obstetric risk in early pregnancy shows promise for reducing caesarean births.

Mercury resistance among clinical isolates of Escherichia coli.

The use of organomercurials in liquid detergents and disinfectants promoted resistance to mercury among bacteria. Dental amalgam and industries using mercury are the main source of human exposure to mercury vapor. Release of mercury from dental amalgam contributes to the enrichment of the intestinal flora with mercury resistance plasmids which may be associated with antibiotic resistance. The aim of our study was to evaluate the frequency of E. coli strains resistant to mercury and other antimicrobial agents currently used in therapy. The bacterial mercury and ampicillin, cephalexin, cefotaxime, gentamicin, tetracycline and chloramphenicol resistance was tested against 363 E. coli strains obtained from faeces and urine between 1999-2000. According to the guidelines suggested by NCCLS (1998), minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar, using the dilution technique with an inoculum of about 10(5) CFU. The MICs were read after 18 h incubation at 37 degrees C as the lowest concentration that inhibited the development of visible growth. Plasmids in enterobacteria may carry genes encoding resistance to both mercury and antibiotics. Among the tested E. coli strains, mercury resistance rose to 29.2%. Mercury resistance in E. coli is significantly linked to multiresistance to antimicrobial agents. Between 91.5-23.6 of mercury chloride resistant isolates were also resistant to the tested antibiotics. The increased use of non antibiotic antimicrobial agents is a possible selection factor for antibiotic-resistant strains in clinical and domestic environments.

Team midwifery care in a tertiary level obstetric service: a randomized controlled trial.

BACKGROUND: In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through to the postpartum period was implemented for women attending Monash Medical Centre, a tertiary level obstetric service, in Melbourne, Australia. The objective of this study was to compare the new model of care with standard maternity care. METHODS: In a randomized controlled trial, 1000 women who booked at the antenatal clinic and met the eligibility criteria were randomly allocated to receive continuity of midwifery care (team care) from a group of seven midwives in collaboration with obstetric staff, or care from a variety of midwives and obstetric staff (standard care). The primary outcome measures were procedures in labor, maternal outcomes, neonatal outcomes, and length of hospital stay. RESULTS: Women assigned to the team care group experienced less augmentation of labor, less electronic fetal monitoring, less use of narcotic and epidural analgesia, and fewer episiotomies but more unsutured tears. Team care women stayed in hospital 7 hours less than women in standard care. More babies of standard care mothers were admitted to the special care nurseries for more than 5 days because of preterm birth, and more babies of team care mothers were admitted to the nurseries for more than 5 days with intrauterine growth retardation. No differences occurred in perinatal mortality between the two groups. CONCLUSIONS: Continuity of midwifery care was associated with a reduction in medical procedures in labor and a shorter length of stay without compromising maternal and perinatal safety. Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service.

Influence of solvents and detergents on matrix-assisted laser desorption/ionization mass spectrometry measurements of proteins and oligonucleotides.

The effect of solvents was found to be critical for sample preparation in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). For proteins and oligonucleotides the use of 2-propanol/water as a solvent for different matrices can significantly improve the quality of spectra. This effect is demonstrated with proteins ranging in molecular weight from 12 to 150 kDa and with a special 19-mer oligonucleotide. A comparison of MALDI-MS using of 2-propanol as matrix solvent and high-performance capillary electrophoresis resulted in identical relative peak intensities for a p(dT)12-18 oligonucleotide mixture. Additionally, the effect of detergents for characterization of high molecular weight proteins in very dilute solutions was studied with this solvent. It was found that Triton X-100, up to a concentration of 1%, was highly compatible with MALDI measurements and even could improve the quality of spectra. Use of detergents for cell profiling has extended the detectable mass range to about m/z 75,000.

Neutrophil inhibitory factor prevents neutrophil-dependent lung injury.

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.

The safety of team midwifery: the first decade of the Monash Birth Centre.

OBJECTIVE: To review the safety of team midwifery care, in terms of perinatal mortality, for pregnant women assessed at their first visit as being at low risk of complications. DESIGN: A cohort study. SETTING: Team midwifery unit (Birth Centre) in a tertiary hospital. PATIENTS: All women who made a booking and met the selection criteria at their first antenatal visit (3085), excluding those with spontaneous or induced fetal loss before 20 weeks (89) and those who withdrew at their own request to seek an alternative form of care (138); the 2858 remaining women gave birth to 2874 infants. MAIN OUTCOME MEASURES: Perinatal mortality rate; and birthweight specific perinatal mortality ratio with reference values being specific rates for birthweight in Victoria for 1984-1985. RESULTS: The perinatal mortality rate was 7.7 per 1000 births (95% confidence interval [CI] 4.8-11.6) for the whole cohort; for women beginning labour in the Birth Centre it was 1.3 per 1000 births (95% CI, 0.3-3.9). The birthweight standardised perinatal mortality ratio was 80 (95% CI, 50-122). CONCLUSION: Within this setting, with explicit criteria for booking and referral, and a framework for consultation, team midwifery care is as safe as the standard maternity care provided within the State.

The role of depressive disorder in the suicidal behavior of alcoholics.

In order to examine the role depressive disorders play in the genesis of suicidal behavior of alcoholics, 330 alcoholic inpatients were examined. Within the total sample, 41% had distinct suicidal tendencies, and of those, 15% had made at least one serious suicide attempt. The MADRS and MMPI scales were used to obtain objective evaluation of the depressive disorders. The subjects were classified according to DSM-R criteria. The results show that suicidal alcoholics have statistically significantly more depressive characteristics.

Factor analytic study of depressive disorders.

Factor analysis was performed on 39 variables (symptoms and characteristics) of a diagnostically heterogenous population of depressive patients (N = 200). The results indicated the existence of one general factor that groups together "endogenomorphous" symptoms and characteristics and three others that are associated with three subtypes of depressive disorders-psychotic, anxiety, and retarded depression. The 13 variables that have high loadings with the first factor agree with widely known facts about the structure of the axial syndrome of endogenous depression.

Birth centre confinement at the Queen Victoria Medical Centre: four years' experience.

A review of the first four years of the functioning of the birth centre at the Queen Victoria Medical Centre is presented. In that time, 1040 pregnant women were accepted for confinement there. Of these, 52 withdrew for non-obstetric reasons, while 470 were transferred to alternative obstetrical care--274 because of antepartum complications and 196 because of intrapartum problems. Therefore, 518 women were delivered in the birth centre. The care of the women is entrusted almost entirely to a team of midwives and this review demonstrates an enviable safety record.