Role of late amniocentesis in the era of modern genomic technologies.

OBJECTIVE: Traditionally, amniocentesis is performed between 17 and 23 weeks of gestation. This enables decisions regarding the course of pregnancy to be made before viability. Less frequently, amniocentesis is performed in the third trimester. Advanced genomic technologies such as chromosomal microarray analysis (CMA) provide more detailed information about the fetus compared with traditional G-banded chromosomal analysis. The aim of this study was to assess the indications for and safety of late amniocentesis, genetic-test results (especially in the context of CMA technology) and outcome of pregnancies that underwent the procedure after 24 weeks. METHODS: Medical records were analyzed retrospectively of all women in whom amniocentesis was performed at a gestational age of 24 + 0 to 38 + 6 weeks, at Hadassah Medical Center, between June 2013 and March 2017. Parameters investigated included indications for late amniocentesis, complications, CMA results and pregnancy outcome. RESULTS: During the study period, 291 women (303 fetuses, 277 singleton and 14 twin pregnancies; in two twin pairs, one fetus was terminated before amniocentesis) underwent late amniocentesis. CMA was performed in all instances of amniocentesis. The most frequent indication was abnormal sonographic finding(s) (204/303 fetuses, 67%). Preterm delivery occurred in 1.7% and 5.1% of pregnancies within the first week and within 1 month following the procedure, respectively. Aneuploidy was detected in nine (3%) fetuses and nine (3%) others had a pathogenic/likely pathogenic copy number variant, suggesting that CMA doubled the diagnostic yield of traditional karyotyping. Maximal diagnostic yield (17.5%) was achieved for the subgroup of fetuses referred with abnormal sonographic findings in two or more fetal anatomical systems. Variants of uncertain significance or susceptibility loci were found in another nine (3%) fetuses. CONCLUSIONS: In pregnancies undergoing late amniocentesis, CMA increased detection rates of fetal abnormalities and had a shorter turnaround time compared with traditional chromosomal analysis; therefore, late amniocentesis may serve as a helpful tool for detecting fetal abnormalities or reassuring parents following late-appearing abnormal sonographic findings. However, CMA may expose findings of uncertain significance, about which the couple should be precounseled. The procedure appears to be safe. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The use of coronary revascularisation procedures in urban Australian Aboriginals and a matched general population coronary procedures in Aboriginals.

BACKGROUND: Coronary revascularisation procedures may be under-used for Aboriginal Australians with ischaemic heart disease (IHD). We compared the use of procedures in an urban Aboriginal population and a non-Aboriginal external comparison group. METHODS: The Perth Aboriginal Atherosclerosis Risk (PAARS) cohort (n=998) and 3695 age- and sex-matched non-Aboriginals were electronically linked to Western Australian hospital morbidity data to identify admissions and revascularisation procedures between 1980 and 2006. RESULTS: There were 731 admissions for IHD for 983 PAARS participants with hospital admissions and 391 in 3150 non-Aboriginals. There were 136 first procedures overall; 43% of Aboriginals having a procedure were women versus 18.5% of non-Aboriginals. 41% of Aboriginal patients and 48% of non-Aboriginals had procedures (p=0.12). Aboriginals were more likely to have coronary artery bypass grafts (CABG) (40.5%) than a percutaneous coronary intervention (PCI), compared to the general population (23%, p=0.02). The proportion of first procedures for acute coronary syndrome (ACS) admissions was 61% for both groups, 80% and 85%, respectively, being PCI. CONCLUSIONS: Coronary revascularisation procedures for IHD were used with equal frequency in Aboriginal people and matched non-Aboriginals. Aboriginal people were more likely to have CABG than PCI. Revascularisation rate and type in ACS admissions were the same.

In vitro techniques for avoiding edge damage in studies of frog skin.

Frog skins mounted between chambers without compression, with a liquid insulator and a tissue adhesive, were studied in vitro. Since voltage and electrical resistance per unit area were unchanged by a tenfold decrease in area of skin studied, it is concluded that these mounting techniques do not produce edge damage and consequently provide a means for study of the skin in its absence.

Measuring the gap: accuracy of the Western Australian hospital morbidity data in the identification of adult urban Aboriginal and Torres Strait Islander people.

OBJECTIVE: To assess the sensitivity of the recording of Aboriginality in the Western Australia Linked Data. METHODS: This was a follow-up study using record linkage. Demographic data was obtained from 993 adult, urban-dwelling Aboriginal Australian participants in the Perth Aboriginal Atherosclerosis Risk study (PAARS). These were linked to the Western Australian Linked Data (State-wide hospital admissions and discharges, and deaths) to provide the number of admissions and Indigenous status coding from 1980 to 2006. RESULTS: There were 14,413 admissions for PAARS participants in the study period. The sensitivity of coding of Indigenous status in hospital admissions data significantly improved over time, exceeding 0.9 in every year since 2002. Prior to 2002 sensitivity was around 0.8, but poorer for males, with some anomalous years. CONCLUSIONS: The coding of Indigenous status in the Western Australia Hospital Morbidity Database since 2002 has improved. The data from earlier decades must be approached with more caution. IMPLICATIONS: The improved accuracy of identification of Indigenous status in the Western Australia Hospital Morbidity Database allows comparative studies of adult Aboriginal and non-Aboriginal population health outcomes to be undertaken with confidence.

Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries in Public Housing.

INTRODUCTION: Caries experience among preschool-age children has remained relatively unchanged for the past 2 decades, despite recently documented decreases in untreated decay. OBJECTIVES: In a community-based cluster-randomized controlled trial, a motivational interviewing (MI) intervention administered to primary caregivers was hypothesized to reduce caries increment over 2 y as compared with controls, among children aged 0 to 5 y at baseline living in public housing. METHODS: Public housing residents, who served as interventionists, were trained in MI with a focus on early childhood caries prevention. All 26 eligible public housing developments were randomized to either control (quarterly clinical examinations, fluoride varnish applications, toothbrush/toothpaste, and educational brochures) or intervention (same procedures as control plus MI counseling). Quarterly MI sessions were delivered in English or Spanish over 2 y, audio recorded, and assessed for treatment fidelity. The primary outcome was the increment in dmfs (decayed, missing, and filled tooth surfaces) as assessed by clinical examination at baseline, 12 mo, and 24 mo. Secondary outcomes included caregiver oral health knowledge and child oral health behaviors (child toothbrushing and sugar-sweetened beverage intake). Baseline characteristics were compared between groups and adjusted for housing-site clusters. Longitudinal outcomes were analyzed with mixed models. RESULTS: A total of 1,065 children (49% female, 55% non-White, 61% Hispanic, 89% below poverty level, n = 686 control) and their caregivers were enrolled. During 2 y of follow-up, the mean dmfs increment increased in both groups; however, there were no statistically significant group differences at 24 mo or group × time interactions. The mean increase in intervention caregivers' knowledge was significantly greater than that of control, F(2, 1,593) = 3.48, P = 0.0310, but there were no significant intervention effects on caregiver-reported child sugar-sweetened beverage intake or child toothbrushing. CONCLUSION: MI counseling plus intensive caries prevention activities resulted in knowledge increases but did not improve oral health behaviors or caries increment (ClinicalTrials.gov NCT01205971). KNOWLEDGE TRANSFER STATEMENT: When viewed in light of the findings from the companion Pine Ridge study and other recent MI studies, the results of this study suggest that when the complex disease of early childhood caries is addressed in high-risk populations, MI is not effective, and alternative approaches are warranted.

Plasma vitamin concentrations and incidence of mesothelioma and lung cancer in individuals exposed to crocidolite at Wittenoom, Western Australia.

Increased rates of death from asbestos-related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom (Western Australia). The relationships between plasma concentrations of retinol, carotene and vitamin E and incidence of mesothelioma and lung cancer in a cohort of people from this town were examined. The relationships were evaluated by survival analyses using data obtained at the first visit, at each visit and with the rate of change of each vitamin during the period of follow-up. Of 1953 study participants, 65 developed mesothelioma during the follow-up, and 47 developed lung cancer. A lower incidence of mesothelioma was related to plasma concentrations of retinol at the first visit [hazard ratio (HR)=0.63, 95% confidence interval=0.41-0.99], and to measurements at each visit (HR=0.71, 95% confidence interval=0.50-1.00). Plasma carotene concentrations at the first measurement, but not during the follow-up period, were associated with lower incidence of lung cancer in men and in workers. No significant associations were found between carotene concentrations and incidence of mesothelioma. Vitamin E concentrations were not significantly associated with mesothelioma or lung cancer incidence. These findings suggest that people with chronically low plasma levels of retinol have increased risk of developing mesothelioma and lung cancer.

Which women stop smoking during pregnancy and the effect on breastfeeding duration.

BACKGROUND: Cigarette smoking during pregnancy increases the risk of adverse pregnancy outcomes and women who quit smoking at this time are able to reduce the risk of low birth weight, preterm labour, spontaneous abortion and perinatal death. This study investigates the socio-demographic characteristics of pregnant women who stop smoking during pregnancy and the association between stopping smoking and breastfeeding duration. METHODS: A 12 month longitudinal study was conducted in two public maternity hospitals in Perth, Australia between mid-September 2002 and mid-July 2003. While in hospital, participating mothers completed a self-administered baseline questionnaire. Follow up telephone interviews were conducted at 4, 10, 16, 22, 32, 40 and 52 weeks. RESULTS: A total of 587 (55%) mothers participated in the study. Two hundred and twenty six (39%) mothers reported smoking prior to pregnancy and 77 (34%) of these stopped smoking during pregnancy. Women who were pregnant for the first time were twice as likely (OR = 2.05; 95% CI 1.047 - 4.03; p < 0.05) to quit smoking as multiparous women. Women who smoked more than 10 cigarettes per day were significantly less likely to quit smoking during pregnancy (OR = 0.36; 95% CI 0.18 - 0.69; p < 0.05). Women who consumed alcohol before pregnancy were three times more likely to quit smoking (OR = 2.58; 95% CI 1.00 - 6.66; p < 0.05). Quitting smoking during pregnancy was significantly associated with breastfeeding for longer than six months (OR = 3.70; 95% CI 1.55 - 8.83; p < 0.05). CONCLUSION: Pregnancy is a time when many women are motivated to quit smoking and providing targeted smoking cessation interventions at this time, which take into account factors predictive of quitting smoking, are more likely to be successful.

Na+ and K+ transport at basolateral membranes of epithelial cells. I. Stoichiometry of the Na,K-ATPase.

The stoichiometry of pump-mediated Na/K exchange was studied in isolated epithelial sheets of frog skin. 42K influx across basolateral membranes was measured with tissues in a steady state and incubated in either beakers or in chambers. The short-circuit current provided estimates of Na+ influx at the apical membranes of the cells. 42K influx of tissues bathed in Cl- or SO4-Ringer solution averaged approximately 8 microA/cm2. Ouabain inhibited 94% of the 42K influx. Furosemide was without effect on pre-ouabain-treated tissues but inhibited a ouabain-induced and Cl--dependent component of 42K influx. After taking into account the contribution of the Na+ load to the pump by way of basolateral membrane recycling of Na+, the stoichiometry was found to increase from approximately 2 to 6 as the pump-mediated Na+ transport rate increased from 10 to 70 microA/cm2. Extrapolation of the data to low rates of Na+ transport (less than 10 microA/cm2) indicated that the stoichiometry would be in the vicinity of 3:2. As pump-mediated K+ influx saturates with increasing rates of Na+ transport, Na+ efflux cannot be obligatorily coupled to K+ influx at all rates of transepithelial Na+ transport. These results are similar to those of Mullins and Brinley (1969. Journal of General Physiology. 53:504-740) in studies of the squid axon.

Na+ and K+ transport at basolateral membranes of epithelial cells. II. K+ efflux and stoichiometry of the Na,K-ATPase.

Changes of 42K efflux (J23K) caused by ouabain and/or furosemide were measured in isolated epithelia of frog skin. From the kinetics of 42K influx (J32K) studied first over 8-9 h, K+ appeared to be distributed into readily and poorly exchangeable cellular pools of K+. The readily exchangeable pool of K+ was increased by amiloride and decreased by ouabain and/or K+-free extracellular Ringer solution. 42K efflux studies were carried out with tissues shortcircuited in chambers. Ouabain caused an immediate (less than 1 min) increase of the 42K efflux to approximately 174% of control in tissues incubated either in SO4-Ringer solution or in Cl-Ringer solution containing furosemide. Whereas furosemide had no effect on J23K in control tissues bathed in Cl-rich or Cl-free solutions, ouabain induced a furosemide-inhibitable and time-dependent increase of a neutral Cl-dependent component of the J23K. Electroconductive K+ transport occurred via a single-filing K+ channel with an n' of 2.9 K+ efflux before ouabain, normalized to post-ouabain (+/- furosemide) values of short-circuit current, averaged 8-10 microA/cm2. In agreement with the conclusions of the preceding article, the macroscopic stoichiometry of ouabain-inhibitable Na+/K+ exchange by the pump was variable, ranging between 1.7 and 7.2. With increasing rates of transepithelial Na+ transport, pump-mediated K+ influx saturated, whereas Na+ efflux continued to increase with increases of pump current. In the usual range of transepithelial Na+ transport, regulation of Na+ transport occurs via changes of pump-mediated Na+ efflux, with no obligatory coupling to pump-mediated K+ influx.

Na+ and K+ transport at basolateral membranes of epithelial cells. III. Voltage independence of basolateral membrane Na+ efflux.

Na+ efflux across basolateral membranes of isolated epithelia of frog skin was tested for voltage sensitivity. The intracellular Na+ transport pool was loaded with 24Na from the apical solution and the rate of isotope appearance in the basolateral solution (JNa23) was measured at timed intervals of 30 s. Basolateral membrane voltage was depolarized by either 50 mM K+, 5 mM Ba++, or 80 mM NH+4. Whereas within 30 s ouabain caused inhibition of JNa23, depolarization of Vb by 30-60 mV caused no significant change of JNa23. Thus, both pump-mediated and leak Na+ effluxes were voltage independent. Although the pumps are electrogenic, pump-mediated Na+ efflux is voltage independent, perhaps because of a nonlinear relationship between pump current and transmembrane voltage. Voltage independence of the leak Na+ efflux confirms a previous suggestion (Cox and Helman, 1983. American Journal of Physiology. 245:F312-F321) that basolateral membrane Na+ leak fluxes are electroneutral.