A way forward for fundamental physics in space.

Space-based research can provide a major leap forward in the study of key open questions in the fundamental physics domain. They include the validity of Einstein's Equivalence principle, the origin and the nature of dark matter and dark energy, decoherence and collapse models in quantum mechanics, and the physics of quantum many-body systems. Cold-atom sensors and quantum technologies have drastically changed the approach to precision measurements. Atomic clocks and atom interferometers as well as classical and quantum links can be used to measure tiny variations of the space-time metric, elusive accelerations, and faint forces to test our knowledge of the physical laws ruling the Universe. In space, such instruments can benefit from unique conditions that allow improving both their precision and the signal to be measured. In this paper, we discuss the scientific priorities of a space-based research program in fundamental physics.

Haematological parameters associated with postpartum haemorrhage after vaginal delivery: Results from a French cohort study.

BACKGROUND: Immediate postpartum haemorrhage (PPH) is a major, feared and often unpredictable issue. Besides many clinical risk factors, some biological parameters could also be predictive of PPH. OBJECTIVE: To study simple and easily accessible haematological parameters as potential risk factors for PPH after vaginal delivery. METHODS: All women who had a vaginal delivery between April 1, 2013 and May 29, 2015 in the maternity ward of Brest University Hospital (France) were included, after oral informed consent obtained. Clinical data were collected by obstetricians or midwives during antenatal care visits, labour and delivery, and recorded by trained research assistants. Haematological variables, including immature platelet fraction, were measured from a blood sample systematically collected at the entrance in the delivery room. PPH, measured with a graduated collector bag, was defined as blood loss of at least 500 ml. RESULTS: 2742 women were included. PPH occurred in 141 (5%) women. Seven clinical factors were independently associated with PPH: pre-eclampsia (OR 5.85, 95%CI 2.02, 16.90), multiple pregnancy (OR 3.28, 95%CI 1.21, 8.91), assisted reproduction (OR 2.75, 95%CI 1.45, 5.20), antepartum bleeding (OR 2.15, 95%CI 1.24,3.73), post-term delivery (OR 1.93, 95%CI 1.17, 3.17), obesity (OR 2.95, 95%CI 1.76, 4.93) and episiotomy (OR 2.51, 95%CI 1.63, 3.74). Three haematological factors were additionally identified as independent risk factors for PPH: platelets < 150 Giga/L (OR 2.98, 95%CI 1.63, 5.46), fibrinogen < 4.5 g/l (OR 1.86, 95%CI 1.21, 2.87) and APTT ratio ≥ 1.1 (OR 2.16, 95%CI 1.31, 3.57). Immature platelet fraction was not associated with PPH. CONCLUSION: Besides classical clinical risk factors, this study identifies simple haematological parameters as risk factors for PPH.

Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice.

BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.

Effect of drug incorporation technique and polymer combination on the performance of biopolymeric antifungal buccal films.

Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.

Formulation and in-vitro efficacy of antifungal mucoadhesive polymeric matrices for the delivery of miconazole nitrate.

Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures.

Role of Exosomes in Placental Homeostasis and Pregnancy Disorders.

The human placenta is a unique organ that performs the function of the majority of fetal organs across gestation. How the placenta communicates with maternal tissues to prepare them for pregnancy is not fully understood. Recently, it has been established that placental cells can communicate with maternal tissues to regulate their biological function via extracellular vesicles (EVs). EVs are subclassified into exosomes or microvesicles (MVs) according to their size, cell or tissue of origin, functions, and physical features. Exosomes are a specific type of EVs from an endocytic origin, while MVs are released via budding from the plasma membrane. With regards to pregnancy, the role of EVs has been described in several functions such as immune responses and maternal metabolic adaptation to gestation. Interestingly, EVs of placental origin can be detected in a variety of body fluids including urine and blood, and have been identified in the maternal circulation at as early as 6 weeks of gestation. Moreover, the number of exosomes across gestation is higher in complications of pregnancies such as preeclampsia and gestational diabetes mellitus compared to normal pregnancies. Circulating exosomes contains proteins and RNAs that are representative of the cell of origin, including surface and cytoplasmic protein, messenger RNA, and micro-RNAs. Finally, exosomes are capable of transferring their contents to other cells and regulating the biological function of the target cell. In this review, we will discuss the effect of the maternal microenvironment on secretion and content of placenta-derived EVs, and how this may lead to complications of pregnancies with a special emphasis on exosomes.

Development and Evaluation of Buccal Films Based on Chitosan for the Potential Treatment of Oral Candidiasis.

In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.

Plasma exosome profiles from dairy cows with divergent fertility phenotypes.

Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes. Plasma was obtained and characterized on the basis of genetic ancestry as fertile (FERT; <23% North American genetics, New Zealand Holstein-Friesian strain, n=8) or subfertile (SUBFERT; >92% North American genetics, North American Holstein-Friesian strain, n=8). Exosomes were isolated by differential and buoyant density centrifugation and characterized by size distribution (nanoparticle tracking analysis, NanoSight NS500, NanoSight Ltd., Amesbury, UK), the presence of CD63 (Western blot), and their morphology (electron microscopy). The total number of exosomes was determined by quantifying the immunoreactive CD63 (ExoELISA kit, System Biosciences), and the protein content established by mass spectrometry. Enriched exosome fractions were identified as cup-shape vesicles with diameters around 100 nm and positive for the CD63 marker. The concentration of exosomes was 50% greater in FERT cows. Mass spectrometry identified 104 and 117 proteins in FERT and SUBFERT cows, of which 23 and 36 were unique, respectively. Gene ontology analysis revealed enrichment for proteins involved in immunomodulatory processes and cell-to-cell communication. Although the role of exosomes in dairy cow reproduction remains to be elucidated, their quantification and content in models with divergent fertility phenotypes could provide novel information to support both physiological and genetic approaches to improving dairy cow fertility.

[Traffic accidentability and risky driving behavior in young people in New Caledonia. Results of study Situation Sociale et Comportements de Santé des Jeunes en Nouvelle-Calédonie]. / Accidentalité et prise de risque sur la route en Nouvelle-Calédonie. Résultats de l'étude Situation sociale et comportements de santé des jeunes en Nouvelle-Calédonie.

BACKGROUND: New Caledonia has one of the highest global rates of death from road accidents: 240 deaths per million inhabitants in 2011 with a majority of young people. However, research on driving behaviors has remained rare. METHODS: A cross-sectional survey based on face-to-face questionnaire with 1400 male and female youth aged 16 to 25 was conducted in 2007. It was used to measure the frequency of accidents and to compute a score of driving behaviors and their associations with socio-demographic characteristics, lifestyles as well as other health behaviors. RESULTS -  CONCLUSION: A total of 10.6% of boys and 6.5% of girls reported a car accident in the previous twelve months period. Among male participants risky driving behavior was associated with having a degree (ORa=2, 95% CI [1.1-3.8]), sport practices (ORa=3.7, 95% CI [1.9-7.05]), involvement in a fight in the last twelve months (ORa=2.2, 95% CI [1.4-3.4]) and precocity of cannabis use (ORa=1.8, 95% CI [1.2-2.8]). Youth living in couple and those with children presented with higher risk-taking scores. Among female participants, young age at cannabis initiation (ORa=3.1, 95% CI [1.5-6.4]) and at sexual debut (ORa=2.4, 95% CI [1.1-5.1]) were associated with driving risk-taking. Finally, younger age at first alcohol intoxication was associated with risky behavior on the road in both sexes. These results highlighted the multidimensional nature of risk-taking behaviors on the road and showed that they are part of, for boys and girls, a larger pattern of risky behaviors. Such results suggest to include behaviors on the road in a comprehensive approach of prevention.

IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid.

Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology; 2) xenobiotics and endocrine disruptors and pregnancy; 3) lipid mediators and placental function.

Modulation of intracellular pH in human ovarian cancer.

To sustain tumor growth, the cancer cells need to adapt to low levels of oxygen (i.e., hypoxia) in the tumor tissue and to the tumor-associated acidic microenvironment. In this phenomenon, the activation of the sodium/proton exchanger 1 (NHE1) at the plasma membrane and the hypoxia-inducible factor (HIF) are critical for the control of the intracellular pH (pHi) and for hypoxia adaptation, respectively. Interestingly, both of these mechanisms end in sustaining cancer cell proliferation. However, regulatory mechanisms of pHi in human ovary tissue and in malignant ascites are unknown. Additionally, a potential role of NHE1 in the modulation of H(+) efflux in human ovarian cancer cells is unknown. In this review, we discussed the characteristics of tumor microenvironment of primary human ovarian tumors and tumor ascites, in terms of pHi regulatory mechanisms and oxygen level. The findings described in the literature suggest that NHE1 may likely play a role in pHi regulation and cell proliferation in human ovarian cancer, potentially involving HIF2α activation. Since ovarian cancer is the fifth cause of prevalence of women cancer in Chile and is usually of late diagnosis, i.e., when the disease jeopardizes peritoneal cavity and other organs, resulting in reduced patient survival, new efforts are required to improve patient-life span and for a better understanding of the pathophysiology of the disease. The potential advantage of the use of amiloride and amiloride-derivatives for cancer treatment in terms of NHE1 expression and activity is also discussed as a therapeutic approach in human ovarian cancer.

Pulmonary drug delivery: a review on nanocarriers for antibacterial chemotherapy.

As the WHO stated, lower respiratory infections are the third leading cause of death. In addition, it is remarkable that antimicrobial resistance represents a huge threat. Thus, new therapeutic weapons are required. Among the possible alternatives, antibiotic encapsulation in nanoparticles has gained much attention in terms of improved tolerability, activity and ability to combat the resistance mechanisms of bacteria. In this regard, this review article focuses on the latest nanocarrier approaches for inhalatory therapy of antibiotics. First, the technology related to lung disposition will be reviewed. Then, nanocarrier systems will be introduced and the challenges required to perform adequate pulmonary deposition analysed. In the following part, drug delivery systems (DDSs) on the market or in clinical trials are described and, finally, new approaches of nanoparticles that have reached pre-clinical stage are enumerated. Altogether, this review aims at gathering together the novel nanosystems for anti-infectious therapy, underlining the potential of DDSs to improve and optimize currently available antibiotic therapies in the context of lung infections.

IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

Myostatin in the placentae of pregnancies complicated with gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is characterised by maternal glucose intolerance and insulin resistance during pregnancy. Myostatin, initially identified as a negative regulator of muscle development may also function in the regulation of placental development and glucose uptake. Myostatin expression in placentae of GDM complicated pregnancies is unknown. However, higher myostatin levels occur in placentae of pregnancies complicated with preeclampsia. We hypothesise that myostatin will be differentially expressed in GDM complicated pregnancies. METHODS: Myostatin concentrations (ELISA) were evaluated in plasma of presymptomatic women who later developed GDM and compared to plasma of normal glucose tolerant (NGT) women. Furthermore, myostatin protein expression (Western blot) was studied in placentae of pregnant women with GDM (treated with diet or insulin) compared to placentae of NGT women. RESULTS: No significant difference in myostatin concentration was seen in plasma of pre-symptomatic GDM women compared to NGT women. In placenta significant differences in myostatin protein expressions (higher precursor; p < 0.05and lower dimer: p < 0.005) were observed in GDM complicated compared to NGT pregnancies. Furthermore, placentae of GDM women treated with insulin compared to diet have higher dimer (p < 0.005) and lower precursor (p < 0.05). Compared to lean women, placentae of obese NGT women were lower in myostatin dimer expression (p < 0.05). DISCUSSION: Myostatin expression in placental tissue is altered under stress conditions (e.g. obesity and abnormal glucose metabolism) found in pregnancies complicated with GDM. We hypothesise that myostatin is active in these placentae and could affect glucose homoeostasis and/or cytokine production thereby altering the function of the placenta.

[Alfred-Louis-Dominique Richet (1816-1891): education, anatomy and surgery]. / Alfred-Louis-Dominique Richet (1816-1891) : pédagogie, anatomie et chirurgie.

Alfred-Louis-Dominique Richet was an anatomist and surgeon born in Dijon, France in 1816. He defended the teaching of clinical anatomy instead of descriptive anatomy, judged inappropriate to learn operative medicine. His name is associated with several anatomical structures that we cite in the present article.

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. Of the 88 participants who reported at least one discontinuation attempt, over half (n = 47, 54.7%) reported stopping without clinician knowledge or support. This group was 35% (confidence interval 15.4-54.6%) more likely to stop abruptly than those (n = 41, 45.3%) stopping with clinician support (P = 0.002). Only 10 participants (23.3%) recalled being given information about discontinuation symptoms other than relapse; however, 68 participants (78.2%) reported experiencing a range of discontinuation symptoms including physical, cognitive, emotional, psychotic or sleep-related disturbances. Findings cannot be readily generalized because of sampling constraints. However, the significant number of participants who reported discontinuation symptoms, in addition to psychosis, is consistent with previous research. This study provides new insight into consumer motivations for discontinuation and possible problems in clinical communication that may contribute to frequent non-collaborative discontinuation attempts. Mental health nurses, who play a pivotal role in medication communication events, may benefit from increased awareness of consumer perspectives on this topic.

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. We probe the collective dynamics of this system by exciting center-of-mass oscillations that exhibit extremely low damping below a certain critical velocity. Using high-precision spectroscopy of these modes, we observe coherent energy exchange and measure the coupling between the two superfluids. Our observations can be captured theoretically using a sum-rule approach that we interpret in terms of two coupled oscillators.

[Étienne Destot (1864-1918): the first radioanatomist in Lyon, France]. / Étienne Destot (1864-1918) : l'anatomie radiographique.

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. He came back in Lyon as a resident in 1886. Destot worked as an assistant in the laboratory of anatomy of Leo Testut in 1880. His thesis, in 1892, analyzed mortality in the departments of surgery of the Lyon hospitals. The polemical results he presented compromised his surgical career. He went on as prosector by Leo Testut, and then became electrician-physician in 1895 (electrotherapy and galvanotherapy). Étienne Destot of Lyon, France, developed in 1895 the first radiography room ever at the Hôtel-Dieu of Lyon, France. Wilhelm Röntgen discovered the X-rays in the same year, and Destot felt his discovery could revolutionize the approach of anatomy and traumatology. He studied wrist, ankle and calcaneus fractures, and described a new anatomy: "traumatic anatomy". For example, he focused on the posterior talar surface hollow in posterior tarsus fractures. He proposed the term of "thalamus" for this articular surface; this term is nowadays widely used by the clinicians. He introduced the term of "third malleolus" to describe the posterior part of the distal extremity of the tibia. He was the first author to analyze the normal and pathological movements of the scaphoid bone and the lunatum in wrist extension.

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.

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.