A comparison among oscillometric waveforms in healthy nonpregnant women, pregnancy and hypertensive disorders of pregnancy.

OBJECTIVE: Understanding of how oscillometric waveforms (OMW) vary between pregnant and nonpregnant individuals remains low. An exploratory analysis was completed to assess for quantitative and qualitative changes in OMW and oscillometric envelope features in pregnancy. DESIGN AND METHODS: Eighteen pregnant individuals (over 20 weeks gestational age) and healthy, nonpregnant (HNP) women were recruited. Six HNP were matched to six healthy pregnant (HP) women, and six pregnant women with a hypertensive disorder of pregnancy (HDP) by age, arm circumference, and cuff size. Blood pressure measurements were completed per the International Organization for Standardization (ISO) protocol using a custom-built oscillometric device as the test device and two-observer mercury auscultation as the reference measurement. Auscultatory blood pressure and blood pressure derived from slope-based and fixed ratio algorithms were determined. OMW and envelope features were compared among groups. RESULTS: In HNP, HP, and HDP groups respectively: mean auscultatory blood pressure (systolic mean ± SD/diastolic mean ± SD) was 103.4 ±â€…12.2/67.1 ±â€…7.9; 109.5 ±â€…3.1/58.1 ±â€…6.4; 135.6 ±â€…18.9/85.1 ±â€…14.2 mmHg. HDP had significantly higher auscultatory systolic and diastolic blood pressure than the HP group ( P  = 0.001). The pregnant groups had a lower average pulse width (mean ± SD: HNP = 0.8 ±â€…0 s, HP = 0.6 ±â€…0.1 s, HDP = 0.6 ±â€…0.1 s; HP vs. HNP mean difference [adjusted P value]: 0.2 [ P  = 0.004], HDP vs. HNP 0.1 [ P  = 0.018]) compared with the HNP group. The HDP group had a larger area under the OMW envelope than the HNP group (mean ± SD: HNP = 22.6 ±â€…3.4; HDP = 28.5 ±â€…4.2; HDP vs. HNP mean difference [adjusted P value]: 5.9 P  = 0.05). CONCLUSION: In this exploratory work, differences in the OMW morphology and parameters were found in pregnancy and in hypertensive disorders of pregnancy compared with healthy controls. Even small differences may have important implications in algorithm development; further work comparing OMW envelopes in pregnancy is needed to optimize the algorithms used to determine blood pressure in pregnancy.

stillbirth prevention: Raising public awareness of stillbirth in Australia.

Prevention of stillbirth remains one of the greatest challenges in modern maternity care. Despite this, public awareness is low and silence is common within families, the community and even healthcare professionals. Australian families and parent advocacy groups given a voice through the Senate Enquiry have made passionate and articulate calls for a national stillbirth awareness campaign. This fourth paper in the Stillbirth in Australia series outlines why stillbirth needs a national public awareness campaign; and provides an overview of good practice in the design, development and evaluation of public awareness campaigns. The cognitive and affective steps required to move from campaign awareness to action and eventually to stillbirth prevention are described. Using these best practice principles, learning from previous campaigns combined with close collaboration with aligned agencies and initiatives should assist a National Stillbirth Prevention Campaign to increase community awareness of stillbirth, help break the silence and contribute to stillbirth prevention across Australia.

Perceived importance of evidence-based psychosocial clinical guidelines for Hong Kong Chinese women with breast cancer: opinions of patients and health care providers.

AIM: The aim of this study was to assess Chinese breast cancer patients' and health care providers' (HCPs) perceptions of psychosocial clinical guidelines developed by the Australian National Health and Medical Research Council's National Breast Cancer Centre. MATERIALS AND METHODS: A convenience sample of Hong Kong Chinese women diagnosed with breast cancer was recruited. In addition, all surgeons and clinical/medical oncologists registered with the Hong Kong Medical Council were invited to complete a mailed survey. Both women and HCPs were asked to rate the importance of the 55 psychosocial clinical guideline items. HCPs also rated the feasibility of implementing each item in their practice. Overall, 344 of 362 (95%) women completed the face-to-face interview. Of 490 eligible HCPs, 75 (15%) completed the mailed survey. RESULTS: At least 50% of the women rated 16 of the 55 psychosocial issues as an essential part of psychosocial care in clinical practice. The top ten ranked items rated essential by patients addressed disease and treatment information provision and question opportunity. HCPs also placed high priority on the scope and opportunities for information giving. Emotional care was intermediately valued. Practical issues and providing social support were rated by both patients and HCPs as the least important aspect of psychosocial care in clinical practice. Fewer than half of the HCPs rated any psychosocial item as feasible to implement in their practice. CONCLUSIONS: Chinese women value information provision and question opportunities, highlighting the need of HCPs to address these issues. Interventions that facilitate HCP's provision of psychosocial support in breast cancer should be set as a high priority.

Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A.

The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+ (an amino acid transporter with a Na+/Cl(-)-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl-, compatible with hOCTN2 and ATB0+ function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer.

Disruption of pancreatic beta-cell lipid rafts modifies Kv2.1 channel gating and insulin exocytosis.

In pancreatic beta-cells, the predominant voltage-gated Ca(2+) channel (Ca(V)1.2) and K(+) channel (K(V)2.1) are directly coupled to SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor) proteins. These SNARE proteins modulate channel expression and gating and closely associate these channels with the insulin secretory vesicles. We show that K(V)2.1 and Ca(V)1.2, but not K(V)1.4, SUR1, or Kir6.2, target to specialized cholesterol-rich lipid raft domains on beta-cell plasma membranes. Similarly, the SNARE proteins syntaxin 1A, SNAP-25, and VAMP-2, but not Munc-13-1 or n-Sec1, are associated with lipid rafts. Disruption of the lipid rafts by depleting membrane cholesterol with methyl-beta-cyclodextrin shunts K(V)2.1, Ca(V)1.2, and SNARE proteins out of lipid rafts. Furthermore, methyl-beta-cyclodextrin inhibits K(V)2.1 but not Ca(V)1.2 channel activity and enhances single-cell exocytic events and insulin secretion. Membrane compartmentalization of ion channels and SNARE proteins in lipid rafts may be critical for the temporal and spatial coordination of insulin release, forming what has been described as the excitosome complex.