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À partir de l’analyse de la littérature scientifique en homéopathie, des propositions sont faites en recherche fondamentale et clinique. La poursuite de ces études scientifiques est essentielle pour maintenir l’intégration de l’homéopathie dans notre système de santé.

The recent evaluation of the efficacy of homeopathic medicines by the French High Authority for Health (HAS) mainly focused on the medicine, yet homeopathy is a therapy which should be evaluated as a whole. After having described the main characteristics of this therapy, the examination of the results obtained in different clinical situations examined by the HAS enables clinical evaluation proposals to be put forward, with observational studies and clinical trials adapted to the therapy's key singularity: the individualisation of the treatment. The continued integration of homeopathic medicine in the French health system and its reimbursement is an essential condition for ensuring the development of research and patient safety.

La récente évaluation de l’efficacité des médicaments homéopathiques par la Haute Autorité de Santé (HAS) a été essentiellement centrée sur le médicament alors que l’homéopathie constitue une thérapeutique qu’il est nécessaire d’évaluer dans son ensemble. Après avoir décrit les caractéristiques essentielles de cette thérapeutique, l’examen des résultats obtenus dans différentes situations cliniques examinées par la HAS permet de faire des propositions d’évaluation clinique, avec des études d’observation et des essais cliniques adaptés à la singularité essentielle de la thérapeutique : l’individualisation du traitement. La poursuite de l’intégration du médicament homéopathique dans le système de santé français et de son remboursement est une condition indispensable pour assurer le développement de la recherche et la sécurité des patients.

Dans un texte essentiel, Denis Demarque décrivait en 1995 la démarche hahnemannienne, ses sources philosophiques, l’application pratique de la similitude à travers l’expérimentation chez l’homme sain, l’évolution vers les doses atténuées et l’interprétation des maladies chroniques, très proche de la médecine classique. Il souligne les limites d’un dogmatisme excessif, préférant pour l’homéopathie la voie de la médecine de l’expérience.

Cet article propose une réflexion sur l’errance, à partir d’un travail d’accompagnement de deux résidentes présentant ce symptôme en institution. Dans un premier temps, nous soulèverons les problématiques conceptuelles concernant la notion de déambulation et leur importance dans le choix du terme « errance ». Ensuite, deux vignettes cliniques seront présentées afin d’analyser l’hypothèse selon laquelle cette activité motrice peut être une modalité d’apaisement de l’angoisse, ou encore, un moyen de faire persister la dimension subjective du sujet. Pour finir, nous soulignerons les limites d’une telle recherche et des difficultés rencontrées par le psychologue lors de l’accompagnement des sujets errants.

Sabadillaest indiqué dans des manifestations digestives et parfois neurologiques, mais c’est surtout dans le cadre des rhinites et sinusites, le plus souvent, mais non exclusivement allergiques, qu’il trouve son indication en homéopathie. Des précisions sémiologiques et l’expérience clinique permettent de souligner l’intérêt de son indication dans l’allergie aux spores de moisissures trop souvent méconnue.

The homeopathic medicine, Siliceahas been used in biological, physico-chemical and clinical studies. In biology, Siliceaincrease the production of paf-acether by mouse peritoneal macrophages. The high dilutions of Siliceahave been studied using nuclear magnetic resonance, with reproducible modifications of water proton relaxation times. It has been used in India for the treatment of tubercular lymphadenitis and could be included in the homeopathic treatment given in addition to the standard care in multi drug resistant pulmonary tuberculosis.

Le médicament homéopathique Siliceaa fait l’objet d’études biologiques, physiques et cliniques. En biologie, Siliceaactive la production de Paf acether par les macrophages péritonéaux de souris. Les hautes dilutions de Siliceaont été étudiées en résonnance magnétique nucléaire avec une modification reproductible des temps de relaxation des protons de l’eau. En clinique, Siliceaa été utilisé en Inde dans le traitement de lymphadénites tuberculeuses et pourrait être inclus dans le traitement homéopathique complémentaire du traitement standard des tuberculoses pulmonaires multirésistantes.

En raison du nombre important de médecins homéopathes en France et des interrogations thérapeutiques que l’homéopathie soulève, le Conseil national de l’Ordre des médecins avait créé, en 1995, une commission d’étude sur l’homéopathie, à l’instigation du Docteur Bernard Glorion. Cette commission, présidée par le docteur Lebatard-Sartre, avait réuni des conseillers ordinaux et des médecins homéopathes, experts et représentatifs des structures afférentes. Au bout de deux années de travail, celle-ci avait publiée, en 1997, un rapport toujours d’actualité, qu’il s’agisse de l’enseignement ou de la recherche.

Entomopathogenic fungi were collected from insects, belonging to orders Lepidoptera, Coleoptera, Hemiptera, Hymenoptera, and Diptera, with signs of infection. Single-spore colonies were identified based on morphological traits and ribosomal ITS sequences. The most commonly found fungi were Fusarium oxysporumSchlechtendal and Beauveria bassiana(Balsamo-Crivelli) Vuillemin. Isolation of Trichoderma atrovirideBisset, Aspergillus flavipes(Bainier and Sartory) Thom and Church, Aspergillus iizukaeSugiyama, Penicillium mallochiiRivera, Urb and Seifert, Penicillium adametzioidesS. Abe ex G. Smith, and Mucor nidicolaMadden, Stchigel, Guarro and Starks associated to insects is reported for the first time. Tests with B. bassianaisolates against Duponchelia fovealisZeller (Lepidoptera: Crambidae), showed high larval mortality in vitro and in greenhouse, demonstrating its potential as biological control agent. Understanding the fungal microbiota from insects can provide promising isolates for use in integrated pest management programs. This is the first report characterizing the mycobiota in insects collected in strawberry crops, and evaluating the pathogenicity of B. bassianaagainst D. fovealis,a pest that causes severe losses to farmers.

Le doyen Pierre Cornillot occupait une place importante et originale au sein du système de santé français. Après avoir rappelé les grandes lignes de sa carrière, nous proposons le texte d’Introduction au tome d’Homéopathie dans l’Encyclopédie des médecines naturelles, texte qui illustre au mieux sa pensée et son action au service de l’homéopathie.

Patients with chronic kidney disease (CKD) are exposed to uremic toxins and have an increased risk of cardiovascular disease. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AHR). These toxins induce a vascular procoagulant phenotype. Here we investigated AHR activation in patients with CKD and in a murine model of CKD. We performed a prospective study in 116 patients with CKD stage 3 to 5D and measured the AHR-Activating Potential of serum by bioassay. Compared to sera from healthy controls, sera from CKD patients displayed a strong AHR-Activating Potential; strongly correlated with eGFR and with the indoxyl sulfate concentration. The expression of the AHR target genes Cyp1A1and AHRRwas up-regulated in whole blood from patients with CKD. Survival analyses revealed that cardiovascular events were more frequent in CKD patients with an AHR-Activating Potential above the median. In mice with 5/6 nephrectomy, there was an increased serum AHR-Activating Potential, and an induction of Cyp1a1mRNA in the aorta and heart, absent in AhR–/–CKD mice. After serial indoxyl sulfate injections, we observed an increase in serum AHR-AP and in expression of Cyp1a1mRNA in aorta and heart in WT mice, but not in AhR–/–mice. Thus, the AHR pathway is activated both in patients and mice with CKD. Hence, AHR activation could be a key mechanism involved in the deleterious cardiovascular effects observed in CKD.

The Australian government recently published a report investigating the effectiveness of homeopathy in many diseases, using as a source systematic reviews of clinical trials in homeopathy. The study of 57 systematic reviews enabled the analysis of 68 pathological conditions. However, this method leads to the exclusion of well conducted trials and sometimes to far too categorical analyses. Moreover, no homeopathic doctor with expertise on the subject took part in this work. Analysing each situation studied by the working group, we provide additional information and put forward proposals to determine in which areas controlled clinical trials or more pragmatic studies can be carried out.

The ribosome translates nucleotide sequences of messenger RNA to proteins through selection of cognate transfer RNA according to the genetic code. To date, structural studies of ribosomal decoding complexes yielding high-resolution data have predominantly relied on experiments performed at cryogenic temperatures. New light sources like the X-ray free electron laser (XFEL) have enabled data collection from macromolecular crystals at ambient temperature. Here, we report an X-ray crystal structure of the Thermus thermophilus30S ribosomal subunit decoding complex to 3.45 Å resolution using data obtained at ambient temperature at the Linac Coherent Light Source (LCLS). We find that this ambient-temperature structure is largely consistent with existing cryogenic-temperature crystal structures, with key residues of the decoding complex exhibiting similar conformations, including adenosine residues 1492 and 1493. Minor variations were observed, namely an alternate conformation of cytosine 1397 near the mRNA channel and the A-site. Our serial crystallography experiment illustrates the amenability of ribosomal microcrystals to routine structural studies at ambient temperature, thus overcoming a long-standing experimental limitation to structural studies of RNA and RNA–protein complexes at near-physiological temperatures.

L’auteur décrit les principaux médicaments homéopathiques rencontrés dans les réactions d’alarme et de confrontation provoquées par le stress.

Bead‐based single platform cytometry technology (SPT) is the gold standard when performing CD4 absolute counting. However, it presents drawbacks as precision depends on various critical steps (for example, pipetting methodology, overtime stability of beads, stability of fluidics, regular recalibration…) and thus requires skilled operators. The fully automated volumetric SPT AQUIOS CL (Beckman Coulter) has recently emerged as an alternative with no need of beads. It may help improving results standardisation and fulfilling requirements for certification (ISO 15189). In this study, we assessed SPT AQUIOS CL performances in accordance to requirements for ISO 15189 accreditation. We evaluated repeatability and reproducibility (precision), bias (trueness), uncertainty (total error), range limits (linearity, quantification, detection limits), and inter‐reagent/inter‐sample contaminations in enumerating CD4+ T‐cells. Concomitantly, we compared AQUIOS CL CD4+ T‐cell values with the results obtained with our routine bead‐based SPT (that is, FC500 Beckman Coulter, bead‐based SPT), on blood samples from 148 patients representative of clinical laboratory routine workload. Every result (repeatability, reproducibility, trueness, total error) was below the acceptable thresholds proposed in international recommendations. Contamination results and range limits (linearity, quantification, and detection limits) were all found perfectly suitable to routine analysis. The comparison between AQUIOS CL and FC500 exhibited excellent correlation and agreement (Pearson R= 0.99, P< 0.001; Lin's concordance correlation coefficient: Lin ρc= 0.991, Cb = 0.999), and Bland‐Altman analysis did not reveal any systematic error. Our results demonstrate that, upon subsequent validation in more routine conditions, the AQUIOS CL could be a suitable tool for clinical flow cytometry laboratories facing accreditation process. © 2016 International Clinical Cytometry Society

Arundo donax, graminée géante, est un médicament homéopathique prescrit dans la rhinite allergique. Il présente également une sémiologie cutanée. En allergologie, la canne de Provence, utilisée pour la fabrication des anches de clarinette et de saxophone provoque des réactions cutanées de contact principalement chez les sujets allergiques aux pollens de graminées. La sémiologie d’Arundo donaxest discutée à la lumière de ces données allergologiques et de la composition de la souche homéopathique.

Understanding the dynamics of biomolecules is the key to understanding their biological activities. Computational methods ranging from all-atom molecular dynamics simulations to coarse-grained normal-mode analyses based on simplified elastic networks provide a general framework to studying these dynamics. Despite recent successes in studying very large systems with up to a 100,000,000 atoms, those methods are currently limited to studying small- to medium-sized molecular systems due to computational limitations. One solution to circumvent these limitations is to reduce the size of the system under study. In this paper, we argue that coarse-graining, the standard approach to such size reduction, must define a hierarchy of models of decreasing sizes that are consistent with each other, i.e., that each model contains the information of the dynamics of its predecessor. We propose a new method, Decimate, for generating such a hierarchy within the context of elastic networks for normal-mode analysis. This method is based on the concept of the renormalization group developed in statistical physics. We highlight the details of its implementation, with a special focus on its scalability to large systems of up to millions of atoms. We illustrate its application on two large systems, the capsid of a virus and the ribosome translation complex. We show that highly decimated representations of those systems, containing down to 1% of their original number of atoms, still capture qualitatively and quantitatively their dynamics. Decimate is available as an OpenSource resource.

ABSTRACTWhen production of bispecific antibodies requires the co-expression and assembly of three or four polypeptide chains, low expression of one chain can significantly limit assembly and yield. κλ bodies, fully human bispecific antibodies with native IgG structure, are composed of a common heavy chain and two different light chains, one kappa and one lambda. No engineering is applied to force pairing of the chains, thus both monospecific and bispecific antibodies are secreted in the supernatant. In this context, stoichiometric expression of the two light chains allows for maximal assembly of the bispecific antibody. In this study, we selected a κλ body with suboptimal characteristics due to low kappa chain expression. Codon optimization to increase expression of the kappa chain did not improve bispecific yield. Surprisingly, progressive introduction of non-optimal codons into the sequence of the lambda chain resulted in lowering its expression for an optimal tuning of the relative distribution of monospecific and bispecific antibodies. This codon de-optimization led to doubling of the κλ body yield. These results indicate that assembly of different proteins into a recombinant complex is an interconnected process and that reducing the expression of one polypeptide can actually increase the overall yield.

Le docteur Micheline Deltombe, qui a formé des générations de pédiatres homéopathes en France et dans le monde, avait écrit un texte très riche en faveur de l’allaitement maternel, en présentant ses avantages sociaux, psychologiques et préventifs. Elle avait également détaillé de façon très claire et très adaptée à la clinique quotidienne les médicaments homéopathiques indiqués chez la mère et le nourrisson selon la nature des troubles rencontrés lors de l’allaitement maternel. Nous publions en son hommage ce texte qui illustre à la fois sa pratique et sa très grande culture pédiatrique et homéopathique.

Background: Endothelial progenitor cells (EPC) are good candidates for cell‐based therapy in cardiovascular diseases. However, concerns have been raised about the potential risks of EPC‐based cell therapy, in terms of thrombogenicity particularly in inflammatory conditions, currently observed in such patients. Tissue factor (TF) can trigger coagulation and may support thrombogenicity. TF is also a key receptor in angiogenesis. Objective: The present study was designed to (i) evaluate the capacity of resting and tumour necrosis factor‐alpha (TNF)‐α‐stimulated late‐outgrowth endothelial colony‐forming cells (ECFCs) to express TF and (ii) investigate the effect of TF/FVII(a) interaction on procoagulant and non‐procoagulant activities of ECFCs in vitro. Methods:ECFCs from cord blood (cb) and adult peripheral blood (ab) were analyzed for TF expression and activity using reverse transcription‐polymerase chain reaction (RT‐PCR), flow cytometry, Western blot and a thrombin generation assay. Non‐procoagulant properties of TF‐expressing ECFCs were investigated in vitrousing wound‐healing, cell proliferation, tube formation and spheroid‐based assays. Results: ECFCs expressed TF in response to TNF‐α. The up‐regulation of TF conferred to ECFCs a FVII(a)‐dependent thrombin generation activity. Compared with cb‐ECFC, ab‐ECFCs can display a higher level of constitutive TF expression and activity, with a notable heterogeneity among donors. TF/FVIIa interaction did not modify non‐procoagulant properties of TNF‐α stimulated cb‐ECFCs in vitro. Conclusions: Proinflammatory conditions up‐regulate TF expression in ECFCs. This expression confers to ECFCs a strong thrombin generation capacity without influencing their non‐coagulant properties. Our results suggest that EPC‐based cell therapy may be associated with prothrombotic risk which could be limited by inhibiting TF without affecting the proangiogenic capacity of the cells.

With advances in X-ray free-electron lasers (XFELs), serial femtosecond crystallography (SFX) has enabled the static and dynamic structure determination for challenging proteins such as membrane protein complexes. In SFX with XFELs, the crystals are typically destroyed after interacting with a single XFEL pulse. Therefore, thousands of new crystals must be sequentially introduced into the X-ray beam to collect full data sets. Because of the serial nature of any SFX experiment, up to 99% of the sample delivered to the X-ray beam during its “off-time” between X-ray pulses is wasted due to the intrinsic pulsed nature of all current XFELs. To solve this major problem of large and often limiting sample consumption, we report on improvements of a revolutionary sample-saving method that is compatible with all current XFELs. We previously reported 3D-printed injection devices coupled with gas dynamic virtual nozzles (GDVNs) capable of generating samples containing droplets segmented by an immiscible oil phase for jetting crystal-laden droplets into the path of an XFEL. Here, we have further improved the device design by including metal electrodes inducing electrowetting effects for improved control over droplet generation frequency to stimulate the droplet release to matching the XFEL repetition rate by employing an electrical feedback mechanism. We report the improvements in this electrically triggered segmented flow approach for sample conservation in comparison with a continuous GDVN injection using the microcrystals of lysozyme and 3-deoxy-D-manno-octulosonate 8-phosphate synthase and report the segmented flow approach for sample injection applied at the Macromolecular Femtosecond Crystallography instrument at the Linear Coherent Light Source for the first time.