Rhumatologie. Une nouvelle option thérapeutique dans la prise en charge de l'inflammation chronique en rhumatologie: les inhibiteurs des janus kinases [A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)].

In the last 15 years, the therapeutical options for the treatment of chronic inflammatory diseases in rheumatology have increased a lot. Nevertheless, some patients do not respond or respond partially to the current therapies--including to the biologics therapy. Tofacitinib (Xeljanz) is now on the Swiss market. It inhibits the JAK pathway. Tofacitinib--as monotherapy or with methotrexate--improves the control of rheumatoid arthritis (RA). In a comparative study, tofacitinib was as effective as adalimumab. Further, tofacitinib reduced structural damages in RA and is considered as an alternative, in case of non-response, to anti-TNF and probably to other biologics therapy. The side effects are upper respiratory tract and opportunist infections and tuberculosis. Blood count, lipids, kidney function, liver tests, CK and blood pressure have to be monitored.

Troubles digestifs associés aux protozoaires et aux helmintes: prise en charge par le médecin de famille [Gastrointestinal complaints associated to helminth and protozoan: management by the general practitioner].

Protozoan and helminthes are frequently associated with persistent digestive complaints, not only in returning travelers from the tropics, but also in industrialized countries. The symptoms are often more vague than those associated to bacterial or viral infections and diarrhea is not always a key feature of the clinical presentation. Three stool examinations and a full blood cells count looking for eosinophilia is the comer stone of the investigations looking for digestive parasites. This article reviews the epidemiology, clinical presentation, diagnostic and management of digestive protozoans and helminthes.

The effects of electron-hole separation on the photoconductivity of individual metal oxide nanowires

The responses of individual ZnO nanowires to UV light demonstrate that the persistent photoconductivity (PPC) state is directly related to the electron¿hole separation near the surface. Our results demonstrate that the electrical transport in these nanomaterials is influenced by the surface in two different ways. On the one hand, the effective mobility and the density of free carriers are determined by recombination mechanisms assisted by the oxidizing molecules in air. This phenomenon can also be blocked by surface passivation. On the other hand, the surface built-in potential separates the photogenerated electron¿hole pairs and accumulates holes at the surface. After illumination, the charge separation makes the electron¿hole recombination difficult and originates PPC. This effect is quickly reverted after increasing either the probing current (self-heating by Joule dissipation) or the oxygen content in air (favouring the surface recombination mechanisms). The model for PPC in individual nanowires presented here illustrates the intrinsic potential of metal oxide nanowires to develop optoelectronic devices or optochemical sensors with better and new performances.

Multipole modes and spin features in the Raman spectrum of nanoscopic quantum rings

We present a systematic study of ground state and spectroscopic properties of many-electron nanoscopic quantum rings. Addition energies at zero magnetic field (B) and electrochemical potentials as a function of B are given for a ring hosting up to 24 electrons. We find discontinuities in the excitation energies of multipole spin and charge density modes, and a coupling between the charge and spin density responses that allow to identify the formation of ferromagnetic ground states in narrow magnetic field regions. These effects can be observed in Raman experiments, and are related to the fractional Aharonov-Bohm oscillations of the energy and of the persistent current in the ring

Congenital diaphragmatic hernia: current status and review of the literature.

Treatment of congenital diaphragmatic hernia (CDH) challenges obstetricians, pediatric surgeons, and neonatologists. Persistent pulmonary hypertension (PPHT) associated with lung hypoplasia in CDH leads to a high mortality rate at birth. PPHT is principally due to an increased muscularization of the arterioles. Management of CDH has been greatly improved by the introduction of prenatal surgical intervention with tracheal obstruction (TO) and by more appropriate postnatal care. TO appears to accelerate fetal lung growth and to increase the number of capillary vessels and alveoli. Improvement of postnatal care over the last years is mainly due to the avoidance of lung injury by applying low peak inflation pressure during ventilation. The benefits of other drugs or technical improvements such as the use of inhaled nitric oxide or extracorporeal membrane oxygenation (ECMO) are still being debated and no single strategy is accepted worldwide. Despite intensive clinical and experimental research, the treatment of newborn with CDH remains difficult.

Prise en charge des coliques néphrétiques en urgence [Emergency management of renal colic]

Renal colic (RC) is a common problem in primary care practice. It is estimated that 5-12% of the general population will suffer once RC during his lifetime. The primary care physicians play a central role in the management of urolithiasis. This article summarizes the current recommendations in terms of renal colic emergency management: biological assessment, imaging, pain relief and specific treatment. The vast majority of patients only needs efficient antalgic treatment and an outpatient monitoring. A minimal assessment must however be undertaken to detect complicated RC that will require urgent treatment in urology department. The analysis of the stone after the crisis is crucial to set up a preventive treatment.

Hépatite cholestatique persistante sur terbinafine [Terbinafine induced hepatitis with persistent cholestasis]

Nous décrivons un cas d'hépatite cholestatique persistante apparue après un mois de traitement oral par terbinafine pour onychomycose, chez une patiente de 55 ans. Cette femme présente un prurit et un ictère, avec une cholestase sévère plusieurs semaines après l'arrêt de l'antimycosique. Nous excluons une cause infectieuse ou auto-immune. L'histologie d'une biopsie hépatique transjugulaire est compatible avec une réaction immuno-allergique déclenchée par la prise de terbinafine. Nous détaillons les mécanismes d'action de la terbinafine ainsi que sa toxicité hépatique. Nous expliquons la prise en charge et le pronostic d'une hépatite cholestatique d'origine médicamenteuse. La discussion traite du risque d'effets secondaires graves de cette molécule et des précautions à prendre pour le praticien prescripteur.

Comparaison de stratégies thérapeutiques dans la prise en charge de l'hypertension artérielle [Comparison of therapeutic strategies in the management of hypertension]

Guidelines for the treatment of hypertension recommend reducing blood pressure to below 140/90 mmHg. However, there is little to guide the clinician on which pharmacological strategy to pursue: monotherapy with stepped-care, sequential monotherapy, or the initial use of combination therapy. The STRATHE study was designed to clarify this issue by comparing the three strategies. A low-dose combination of perindopril/indapamide was significantly superior to either stepped-care or sequential monotherapy in terms of reducing systolic blood pressure and in the percentage of patients achieving normalisation without adverse effects. Pulse pressure showed a trend to greater reductions with the low-dose combination. Although there must be caution about extrapolating these results to other combinations, which may not have the same pharmacological properties, the STRATHE study has shown that initiating antihypertensive therapy with a low-dose combination has advantages over the two other classical therapeutic strategies.

Correlation between charge transport and electroluminescence properties of Si-rich oxide/nitride/oxide-based light emitting capacitors.

The electrical and electroluminescence (EL) properties at room and high temperatures of oxide/ nitride/oxide (ONO)-based light emitting capacitors are studied. The ONO multidielectric layer is enriched with silicon by means of ion implantation. The exceeding silicon distribution follows a Gaussian profile with a maximum of 19%, centered close to the lower oxide/nitride interface. The electrical measurements performed at room and high temperatures allowed to unambiguously identify variable range hopping (VRH) as the dominant electrical conduction mechanism at low voltages, whereas at moderate and high voltages, a hybrid conduction formed by means of variable range hopping and space charge-limited current enhanced by Poole-Frenkel effect predominates. The EL spectra at different temperatures are also recorded, and the correlation between charge transport mechanisms and EL properties is discussed.

Nouveautés et perspectives dans la prise en charge des cancers colorectaux et gastriques avancés [News and perspectives in the treatment of advanced gastric and colorectal cancers].

Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

Définition et prise en charge de l'échec d'une première injection de toxine botulique Botox(®) 200 U pour hyperactivité détrusorienne neurogène : résultats de l'enquête DETOX [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

OBJECTIVE: There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. METHODS: A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. RESULTS: Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). CONCLUSION: This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U, repeat injection of Botox(®) 300 U should be the first line treatment. Level of proof 4.

Defects in Persistent Luminescence Materials

Persistent luminescence materials can store energy from solar radiation or artificial lighting and release it over a period of several hours without a continuous excitation source. These materials are widely used to improve human safety in emergency and traffic signalization. They can also be utilized in novel applications including solar cells, medical diagnostics, radiation detectors and structural damage sensors. The development of these materials is currently based on methods based on trial and error. The tailoring of new materials is also hindered by the lack of knowledge on the role of their intrinsic and extrinsic lattice defects in the appropriate mechanisms. The goal of this work was to clarify the persistent luminescence mechanisms by combining ab initio density functional theory (DFT) calculations with selected experimental methods. The DFT approach enables a full control of both the nature of the defects and their locations in the host lattice. The materials studied in the present work, the distrontium magnesium disilicate (Sr₂MgSi₂O₇) and strontium aluminate (SrAl₂O₄) are among the most efficient persistent luminescence hosts when doped with divalent europium Eu²⁺ and co-doped with trivalent rare earth ions R³⁺ (R: Y, La-Nd, Sm, Gd-Lu). The polycrystalline materials were prepared with the solid state method and their structural and phase purity was confirmed by X-ray powder diffraction. Their local crystal structure was studied by high-resolution transmission electron microscopy. The crystal and electronic structure of the nondoped as well as Eu²⁺, R^2+/3+ and other defect containing materials were studied using DFT calculations. The experimental trap depths were obtained using thermoluminescence (TL) spectroscopy. The emission and excitation of Sr₂MgSi₂O₇:Eu²+,Dy³⁺ were also studied. Significant modifications in the local crystal structure due to the Eu²⁺ ion and lattice defects were found by the experimental and DFT methods. The charge compensation effects induced by the R³⁺ co-doping further increased the number of defects and distortions in the host lattice. As for the electronic structure of Sr₂MgSi₂O₇ and SrAl₂O₄, the experimental band gap energy of the host materials was well reproduced by the calculations. The DFT calculated Eu²⁺ and R^2+/3+ 4fn as well as 4f^n-15d¹ ground states in the Sr₂MgSi₂O₇ band structure provide an independent verification for an empirical model which is constructed using rather sparse experimental data for the R³⁺ and especially the R²⁺ ions. The intrinsic and defect induced electron traps were found to act together as energy storage sites contributing to the materials’ efficient persistent luminescence. The calculated trap energy range agreed with the trap structure of Sr₂MgSi₂O₇ obtained using TL measurements. More experimental studies should be carried out for SrAl₂O₄ to compare with the DFT calculations. The calculated and experimental results show that the electron traps created by both the rare earth ions and vacancies are modified due to the defect aggregation and charge compensation effects. The relationships between this modification and the energy storage properties of the solid state materials are discussed.

Ultrasonic and Electrokinetic Remediation of Low Permeability Soil Contaminated with Persistent Organic Pollutants

Electrokinetics has emerged as a potential technique for in situ soil remediation and especially unique because of the ability to work in low permeability soil. In electrokinetic remediation, non-polar contaminants like most organic compounds are transported primarily by electroosmosis, thus the process is effective only if the contaminants are soluble in pore fluid. Therefore, enhancement is needed to improve mobility of these hydrophobic compounds, which tend to adsorb strongly to the soil. On the other hand, as a novel and rapidly growing science, the applications of ultrasound in environmental technology hold a promising future. Compared to conventional methods, ultrasonication can bring several benefits such as environmental friendliness (no toxic chemical are used or produced), low cost, and compact instrumentation. It also can be applied onsite. Ultrasonic energy applied into contaminated soils can increase desorption and mobilization of contaminants and porosity and permeability of soil through developing of cavitation. The research investigated the coupling effect of the combination of these two techniques, electrokinetics and ultrasonication, in persistent organic pollutant removal from contaminated low permeability clayey soil (with kaolin as a model medium). The preliminary study checked feasibility of ultrasonic treatment of kaolin highly contaminated by persistent organic pollutants (POPs). The laboratory experiments were conducted in various conditions (moisture, frequency, power, duration time, initial concentration) to examine the effects of these parameters on the treatment process. Experimental results showed that ultrasonication has a potential to remove POPs, although the removal efficiencies were not high with short duration time. The study also suggested intermittent ultrasonication over longer time as an effective means to increase the removal efficiencies. Then, experiments were conducted to compare the performances among electrokinetic process alone and electrokinetic processes combined with surfactant addition and mainly with ultrasonication, in designed cylinders (with filtercloth separating central part and electrolyte parts) and in open pans. Combined electrokinetic and ultrasonic treatment did prove positive coupling effect compared to each single process alone, though the level of enhancement is not very significant. The assistance of ultrasound in electrokinetic remediation can help reduce POPs from clayey soil by improving the mobility of hydrophobic organic compounds and degrading these contaminants through pyrolysis and oxidation. Ultrasonication also sustains higher current and increases electroosmotic flow. Initial contaminant concentration is an essential input parameter that can affect the removal effectiveness.

The molecular basis of selective permeability of connexins is complex and includes both size and charge

Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for biological molecules that are labile within the cell. Of particular relevance to the in vivo function of gap junctions, recent studies are summarized that demonstrate that the connexin phenotype can control the nature of the endogenous traffic between cells, with consequent effects on biological effects of gap junctions such as tumor suppression.

CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells

T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 ± 1.87 ms (N = 16). The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 ± 2.4 and 6.7 ± 0.3 mV (pre-pulse of -120 mV, N = 15), and -27.0 ± 0.97 and 7.5 ± 0.7 mV (pre-pulse of -40 mV, N = 9). The 8-mV shift in the activation mid-point was statistically significant (P < 0.05). The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of a1G (CaV3.1) and a1I (CaV3.3) T-type Ca2+ channel mRNA transcripts.