Experiencing antipsychotic discontinuation: results from a survey of Australian consumers.

Despite high reported rates of antipsychotic non-adherence, little is known about consumer experiences during discontinuation. This study was designed to increase understanding of antipsychotic discontinuation from consumer perspectives. In 2011-2012, 98 Australian consumers involved with participating organizations completed an anonymous survey detailing past antipsychotic discontinuation attempts.

Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration.

Background: Vascular smooth muscle cells (VSMCs) migration is a critical process during human uterine spiral artery (SpA) remodeling and a successful pregnancy. Extravillous trophoblast cells (EVT) interact with VSMC and enhance their migration, however, the mechanisms by which EVT remodel SpA remain to be fully elucidated. We hypothesize that exosomes released from EVT promote VSMC migration.

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy.

Background: Human placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established.

Myostatin is localized in extravillous trophoblast and up-regulates migration.

Context: Myostatin is a highly conserved secretory protein that negatively regulates muscle development by affecting both proliferation and differentiation of muscle cells. In human placentae the expression of myostatin is negatively correlated with gestational age, and in placental explants, myostatin acts to facilitate glucose uptake. Myostatin expression is known to be higher in the placentae of pregnancies complicated by preeclampsia.

A mixture of Bose and Fermi superfluids.

Superconductivity and superfluidity of fermionic and bosonic systems are remarkable many-body quantum phenomena. In liquid helium and dilute gases, Bose and Fermi superfluidity has been observed separately, but producing a mixture in which both the fermionic and the bosonic components are superfluid is challenging. Here we report on the observation of such a mixture with dilute gases of two lithium isotopes, lithium-6 and lithium-7.

Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.

A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity with peak MIC99 values of 2-3 μM for alkyl chains ranging from 10 to 14 carbons in length. Although prior work has linked the function of acridine-based compounds to intercalation and topoisomerase inhibition, the present results show that 9-alkylaminoacridines likely function as amphiphilic membrane-active disruptors potentially in a similar manner as quaternary ammonium antimicrobials.

A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks), second (ST, 22-24 weeks) and third (TT, 32-38 weeks) trimester.

Potential role of A2B adenosine receptors on proliferation/migration of fetal endothelium derived from preeclamptic pregnancies.

To investigate the functionality of A2B adenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies (n = 15) or pregnancies with preeclampsia (n = 15). Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, the A2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level of A2BAR and logEC50 for NECA-mediated proliferation than normotensive pregnancies.

Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported.

[Étienne Destot (1864-1918): the first radioanatomist in Lyon, France].

Destot was born in Dijon, France, in 1864. He began his education in Burgundy, then he started his preclinical curriculum in Lyon, France, from 1884. He had to leave Lyon, and spent some times in Algeria to treat a tuberculosis.

Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines.

The in vitro evaluation of thieno[3,2-d]pyrimidines identified halogenated compounds 1 and 2 with antiproliferative activity against three different cancer cell lines. A structure activity relationship study indicated the necessity of the chlorine at the C4-position for biological activity. The two most active compounds 1 and 2 were found to induce apoptosis in the leukemia L1210 cell line.

Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.

Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)-independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties and potential consequences in hypertension are unknown.

Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200.

Background: The role of exosomes in the pathogenesis and metastatic spread of cancer remains to be fully elucidated. Recent studies support the hypothesis that the release of exosomes from cells modifies local extracellular conditions to promote cell growth and neovascularisation. In addition, exosomes may modify the phenotype of parent and/or target cell.

Subinhibitory antibiotic concentrations mediate nutrient use and competition among soil streptomyces.

Though traditionally perceived as weapons, antibiotics are also hypothesized to act as microbial signals in natural habitats. However, while subinhibitory concentrations of antibiotics (SICA) are known to shift bacterial gene expression, specific hypotheses as to how SICA influence the ecology of natural populations are scarce. We explored whether antibiotic 'signals', or SICA, have the potential to alter nutrient utilization, niche overlap, and competitive species interactions among Streptomyces populations in soil.

IFPA Meeting 2013 Workshop Report I: diabetes in pregnancy, maternal dyslipidemia in pregnancy, oxygen in placental development, stem cells and pregnancy pathology.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy; 2) lipids, fatty acids and the placenta; 3) oxygen in placental development and pathologies; 4) stem cells and pathologies.

IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental development, bioinformatics tools for gene expression analysis, planning and coordination of a placenta research network, placental imaging, evolutionary approaches to understanding pre-eclampsia.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

Realizing a Kondo-correlated state with ultracold atoms.

We propose a novel realization of Kondo physics with ultracold atomic gases. It is based on a Fermi sea of two different hyperfine states of one atom species forming bound states with a different species, which is spatially confined in a trapping potential. We show that different situations displaying Kondo physics can be realized when Feshbach resonances between the species are tuned by a magnetic field and the trapping frequency is varied.

Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes.

Migration of extravillous trophoblasts (EVT) into decidua and myometrium is a critical process in the conversion of maternal spiral arterioles and establishing placenta perfusion. EVT migration is affected by cell-to-cell communication and oxygen tension. While the release of exosomes from placental cells has been identified as a significant pathway in materno-fetal communication, the role of placental-derived exosomes in placentation has yet to be established.

Effects of benznidazole:cyclodextrin complexes on the drug bioavailability upon oral administration to rats.

Benznidazole (BZL) is the drug of choice for the treatment of Chagas' disease, a neglected parasitic infection. It is poorly soluble in water, which may have a direct impact into its bioavailability. Thus, the aim of this study was to evaluate the impact of stoichiometric and non-stoichiometric BZL-cyclodextrins (CDs) complexes on the bioavailability of BZL.

Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a diseases that alters human placenta macro and microvascular reactivity as a result of endothelial dysfunction. The human placenta is a highly vascularized organ which lacks innervation, so blood flux is governed by locally released vasoactive molecules, including the endogenous nucleoside adenosine and the free radical nitric oxide (NO). Altered adenosine metabolism and uptake by the endothelium leads to increased NO synthesis which then turns-off the expression of genes coding for a family of nucleoside membrane transporters belonging to equilibrative nucleoside transporters, particularly isoforms 1 (hENT1) and 2 (hENT2).

Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole, a class II compound.

Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy.

Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.

Vasculogenesis and angiogenesis are critical processes in fetal circulation and placental vasculature development. Placental mesenchymal stem cells (pMSC) are known to release paracrine factors (some of which are contained within exosomes) that promote angiogenesis and cell migration. The aims of this study were: to determine the effects of oxygen tension on the release of exosomes from pMSC; and to establish the effects of pMSC-derived exosomes on the migration and angiogenic tube formation of placental microvascular endothelial cells (hPMEC).

"All roads lead to medication?" Qualitative responses from an Australian first-person survey of antipsychotic discontinuation.

Objective: The purpose of the survey was to better understand the experiences of people who attempt antipsychotic discontinuation.

Method: A multiple-choice and short-answer survey was distributed in 2011-2012 to potential participants involved in participating organizations. Respondents were asked about past discontinuation events, including decision negotiation and withdrawal experience.

Precision measurement of the hydrogen 1S-2S frequency via a 920-km fiber link.

We have measured the frequency of the extremely narrow 1S-2S two-photon transition in atomic hydrogen using a remote cesium fountain clock with the help of a 920 km stabilized optical fiber. With an improved detection method we obtain f(1S-2S)=2466 061 413 187 018 (11)  Hz with a relative uncertainty of 4.5×10(-15), confirming our previous measurement obtained with a local cesium clock [C.