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.

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.

Exploring the thermodynamics of a universal Fermi gas.

One of the greatest challenges in modern physics is to understand the behaviour of an ensemble of strongly interacting particles. A class of quantum many-body systems (such as neutron star matter and cold Fermi gases) share the same universal thermodynamic properties when interactions reach the maximum effective value allowed by quantum mechanics, the so-called unitary limit. This makes it possible in principle to simulate some astrophysical phenomena inside the highly controlled environment of an atomic physics laboratory. Previous work on the thermodynamics of a two-component Fermi gas led to thermodynamic quantities averaged over the trap, making comparisons with many-body theories developed for uniform gases difficult. Here we develop a general experimental method that yields the equation of state of a uniform gas, as well as enabling a detailed comparison with existing theories. The precision of our equation of state leads to new physical insights into the unitary gas. For the unpolarized gas, we show that the low-temperature thermodynamics of the strongly interacting normal phase is well described by Fermi liquid theory, and we localize the superfluid transition. For a spin-polarized system, our equation of state at zero temperature has a 2 per cent accuracy and extends work on the phase diagram to a new regime of precision. We show in particular that, despite strong interactions, the normal phase behaves as a mixture of two ideal gases: a Fermi gas of bare majority atoms and a non-interacting gas of dressed quasi-particles, the fermionic polarons.

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.

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.

[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.

[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.

2.1-watts intracavity-frequency-doubled all-solid-state light source at 671 nm for laser cooling of lithium.

We present an all-solid-state laser source emitting up to 2.1 W of single-frequency light at 671 nm developed for laser cooling of lithium atoms. It is based on a diode-pumped, neodymium-doped orthovanadate (Nd:YVO(4)) ring laser operating at 1342 nm. Optimization of the thermal management in the gain medium results in a maximum multi-frequency output power of 2.5 W at the fundamental wavelength. We develop a simple theory for the efficient implementation of intracavity second harmonic generation, and its application to our system allows us to obtain nonlinear conversion efficiencies of up to 88%. Single-mode operation and tuning is established by adding an etalon to the resonator. The second-harmonic wavelength can be tuned over 0.5 nm, and mode-hop-free scanning over more than 6 GHz is demonstrated, corresponding to around ten times the laser cavity free spectral range. The output frequency can be locked with respect to the lithium D-line transitions for atomic physics applications. Furthermore, we observe parametric Kerr-lens mode-locking when detuning the phase-matching temperature sufficiently far from the optimum value.

Lifetime of the Bose gas with resonant interactions.

We study the lifetime of a Bose gas at and around unitarity using a Feshbach resonance in lithium 7. At unitarity, we measure the temperature dependence of the three-body decay coefficient L(3). Our data follow a L(3)=λ(3)/T(2) law with λ(3)=2.5(3)(stat)(6)(syst)×10(-20) (µK)(2) cm(6) s(-1) and are in good agreement with our analytical result based on zero-range theory. Varying the scattering length a at fixed temperature, we investigate the crossover between the finite-temperature unitary region and the previously studied regime where |a| is smaller than the thermal wavelength. We find that L(3) is continuous across the resonance, and over the whole a<0 range our data quantitatively agree with our calculation.

Pathogen variation and urea influence selection and success of Streptomyces mixtures in biological control.

Success in biological control of plant diseases remains inconsistent in the field. A collection of well-characterized Streptomyces antagonists (n = 19 isolates) was tested for their capacities to inhibit pathogenic Streptomyces scabies (n = 15 isolates). There was significant variation among antagonists in ability to inhibit pathogen isolates and among pathogens in their susceptibility to inhibition. Only one antagonist could inhibit all pathogens, and antagonist-pathogen interactions were highly specific, highlighting the limitations of single-strain inoculum in biological control. However, the collection of pathogens could be inhibited by several combinations of antagonists, suggesting the potential for successful antagonist mixtures. Urea generally increased effectiveness of antagonists at inhibiting pathogens in vitro (increased mean inhibition zones) but its specific effects varied among antagonist-pathogen combinations. In greenhouse trials, urea enhanced the effectiveness of antagonist mixtures relative to individual antagonists in controlling potato scab. Although antagonist mixtures were frequently antagonistic in the absence of urea, all n= 2 and n = 3 antagonist-isolate combinations were synergistic in the presence of urea. This work provides insights into the efficacy of single- versus multiple-strain inocula in biological control and on the potential for nutrients to influence mixture success.

A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing composite pheochromocytoma.

The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is rare. We report on a 45-year-old woman who suffered from persistent secretory diarrhea for six years and who was admitted to hospital with complaints of muscular weakness and myalgia. Biochemical testing revealed pronounced rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long-standing diarrhea including endoscopy of the upper and lower gastrointestinal tract and the small intestine did not show any pathologies. An abdominal computed tomography scan revealed a mass of 4 × 5 cm in the left adrenal gland demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal renin and most prominently VIP were increased in line with a increased 24 hour urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed that was removed surgically. The histological evaluation demonstrated a composite pheochromocytoma. Diarrhea stopped immediately after surgery together with a normalization of laboratory parameters. In conclusion, this case report focuses on the rare clinical presentation of secretory diarrhea and electrolyte disturbances in combination with hypokalemic rhabdomyolysis which was caused by a VIP-producing composite pheochromocytoma.

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.

Fermi-liquid behavior of the normal phase of a strongly interacting gas of cold atoms.

We measure the magnetic susceptibility of a Fermi gas with tunable interactions in the low-temperature limit and compare it to quantum Monte Carlo calculations. Experiment and theory are in excellent agreement and fully compatible with the Landau theory of Fermi liquids. We show that these measurements shed new light on the nature of the excitations of the normal phase of a strongly interacting Fermi gas.

High prevalences of infection with Giardia intestinalis genotype B among children in urban and rural areas of Argentina.

The protozoan parasite most frequently associated with diarrhoea worldwide is Giardia intestinalis. In 2005, a study was initiated to identify the genotypes of this parasite infecting children in the Argentinian provinces of Buenos Aires, Mendoza and Chaco, and to explore the associations between the genotype detected in a child, the characteristics of the child's household and the child's clinical presentation. Overall, 998 children (504 boys and 494 girls) aged between 2-14 years, with or without symptoms, were enrolled. The G. intestinalis in 94 of the 117 stool samples found positive for the parasite by microscopy were successfully genotyped by PCR. Seventy-seven of the children were found to be infected with genotype B only and 14 with genotype AII only, three children being found to have mixed (AII and B) infections. Only genotype B was detected in children from rural areas (P<0·05) and most Giardia detected in children from households with a piped water supply were also of this genotype (P<0·05). The other household characteristics investigated (quality of building, history of flooding, type of sanitation, level of overcrowding, and presence/absence of pet dogs) had no significant effect on the genotype distribution. Children infected with genotype AII were significantly younger than those infected with genotype B (P<0·05) and there was a significant positive association between infection with genotype B and abdominal pain (P<0·05). Diarrhoea was not, however, found to be significantly associated with genotype-AII or genotype-B infection. This is the first published report on the Giardia genotypes circulating in the provinces of Mendoza and Chaco. The results indicate the importance of asymptomatic children in the transmission of Giardia among the young.

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.

[Joseph-Guichard Duverney (1648-1730). Doctor, teacher and researcher in the 17th and 18th centuries]. / Joseph-Guichard Duverney (1648-1730). Médecin, anatomiste et chercheur aux xviie et xviiie siècles.

Duverney was a leader in the field of research and education, because he worked as a physician, as a surgeon and he led many scientific works. To Peltier, he was the first academic professor of surgery. His wonderful career was explained by his heavy interest in knowledge. He became one of the main actors of the scientific revolution of the 17th century, especially concerning the methods of investigation in the medical science. He had so much fear for imperfect purposes, that many scientists of his century called him the Master. The only work he published about the anatomy and physiology of the ear and audition, was a world success, and is still amazing today. During about 50 years, Duverney allowed many advances in the field of osteology, otology, embryology, respiratory and circulatory physiology, but also provided competent pupils as Winslow, Sénac, Petit, Dionis, Valsalva. Duverney is still frequently cited by veterinary and dentists for many descriptions in animal anatomy. He died at the age of 82 years, and worked for the service of science until his death. His legacy consists of many works, some have been used by his pupils to highlight all the benefits he gave to the scientific community.

Acute epiploic appendagitis. Report of three cases.

Primary epiploic appendagitis is a very rare condition that results from acute inflammation of an epiploic appendix. Clinical presentation is non-specific, and many times can mimic acute abdomen. When the diagnosis of epiploic appendagitis is made, conservative treatment must be initiated to avoid unnecessary surgery. We report three cases of acute epiploic appendagitis which were diagnosed by imaging and were managed conservatively with good clinical outcome.

Collective oscillations of an imbalanced Fermi gas: axial compression modes and polaron effective mass.

We investigate the low-lying compression modes of a unitary Fermi gas with imbalanced spin populations. For low polarization, the strong coupling between the two spin components leads to a hydrodynamic behavior of the cloud. For large population imbalance we observe a decoupling of the oscillations of the two spin components, giving access to the effective mass of the Fermi polaron, a quasiparticle composed of an impurity dressed by particle-hole pair excitations in a surrounding Fermi sea. We find m*/m = 1.17(10), in agreement with the most recent theoretical predictions.

[François Chaussier (1746-1828). A vision of the anatomic nomenclature based on education]. / François Chaussier (1746-1828). Une vision de la nomenclature anatomique fondée sur la pédagogie.

François Chaussier (1746-1828) developed an original point of view concerning the anatomic nomenclature teaching and learning. The myology nomenclature proposed by Chaussier was based on a very simple concept: the name of a muscle is composed by its two attachment points. He wanted to make science learning easier for the students; that we can see in his myology nomenclature, his publications and anatomical drawings. His experience is still interesting nowadays.