Changes in Gene Expression After Exposing Arabidopsis thaliana Plants to Nanosecond High Amplitude Electromagnetic Field Pulses.

The biological effects of exposure to electromagnetic fields due to wireless technologies and connected devices are a subject of particular research interest. Ultrashort high-amplitude electromagnetic field pulses delivered to biological samples using immersed electrodes in a dedicated cuvette have widely demonstrated their effectiveness in triggering several cell responses including increased cytosolic calcium concentration and reactive oxygen species (ROS) production. In contrast, the effects of these pulses are poorly documented when electromagnetic pulses are delivered through an antenna. Here we exposed Arabidopsis thaliana plants to 30,000 pulses (237 kV m-1 , 280 ps rise-time, duration of 500 ps) emitted through a Koshelev antenna and monitored the consequences of electromagnetic fields exposure on the expression levels of several key genes involved in calcium metabolism, signal transduction, ROS, and energy status. We found that this treatment was mostly unable to trigger significant changes in the messenger RNA accumulation of calmodulin, Zinc-Finger protein ZAT12, NADPH oxidase/respiratory burst oxidase homolog (RBOH) isoforms D and F, Catalase (CAT2), glutamate-cystein ligase (GSH1), glutathione synthetase (GSH2), Sucrose non-fermenting-related Kinase 1 (SnRK1) and Target of rapamycin (TOR). In contrast, Ascorbate peroxidases APX-1 and APX-6 were significantly induced 3 h after the exposure. These results suggest that this treatment, although quite strong in amplitude, is mostly ineffective in inducing biological effects at the transcriptional level when delivered by an antenna. © 2023 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

Uncovering the Molecular Pathways Implicated in the Anti-Cancer Activity of the Imidazoquinoxaline Derivative EAPB02303 Using a Caenorhabditis elegans Model.

Imiqualines are analogues of the immunomodulatory drug imiquimod. EAPB02303, the lead of the second-generation imiqualines, is characterized by significant anti-tumor effects with IC50s in the nanomolar range. We used Caenorhabditis elegans transgenic and mutant strains of two key signaling pathways (PI3K-Akt and Ras-MAPK) disrupted in human cancers to investigate the mode of action of EAPB02303. The ability of this imiqualine to inhibit the insulin/IGF1 signaling (IIS) pathway via the PI3K-Akt kinase cascade was explored through assessing the lifespan of wild-type worms. Micromolar doses of EAPB02303 significantly enhanced longevity of N2 strain and led to the nuclear translocation and subsequent activation of transcription factor DAF-16, the only forkhead box transcription factor class O (Fox O) homolog in C. elegans. Moreover, EAPB02303 significantly reduced the multivulva phenotype in let-60/Ras mutant strains MT2124 and MT4698, indicative of its mode of action through the Ras pathway. In summary, we showed that EAPB02303 potently reduced the activity of IIS and Ras-MAPK signaling in C. elegans. Our results revealed the mechanism of action of EAPB02303 against human cancers associated with hyperactivated IIS pathway and oncogenic Ras mutations.

Atovaquone exposure and Pneumocystis jirovecii cytochrome b mutations: French data and review of the literature.

Pneumocystis jirovecii is a transmissible fungus responsible for severe pneumonia (Pneumocystis pneumonia [PCP]) in immunocompromised patients. Missense mutations due to atovaquone selective pressure have been identified on cytochrome b (CYB) gene of P. jirovecii. It was recently shown that atovaquone prophylaxis can lead to the selection of specific P. jirovecii CYB mutants potentially resistant to atovaquone among organ transplant recipients. In this context, our objectives were to provide data on P. jirovecii CYB mutants and the putative selective pressure exerted by atovaquone on P. jirovecii organisms in France. A total of 123 patients (124 P. jirovecii specimens) from four metropolitan hospitals and two overseas hospitals were retrospectively enrolled. Fourteen patients had prior exposure to atovaquone, whereas 109 patients did not at the time of P. jirovecii detection. A 638 base-pair fragment of the CYB gene of P. jirovecii was amplified and sequenced. A total of 10 single nucleotide polymorphisms (SNPs) were identified. Both missense mutations C431T (Ala144Val) and C823T (Leu275Phe), located at the Qo active site of the enzyme, were significantly associated with prior atovaquone exposure, these mutations being conversely incidental in the absence of prior atovaquone exposure (P < 0.001). Considering that the aforementioned hospitals may be representative of the national territory, these findings suggest that the overall presence of P. jirovecii CYB mutants remains low in France.

The mutations C431T (Ala144Val) and C823T (Leu275Phe) at the cytochrome b (CYB) active site of Pneumocystis jirovecii are associated with patient prior exposure to atovaquone. Conversely, these mutations are incidental in the absence of exposure. Overall, the presence of P. jirovecii CYB mutants remains low in France.

Recent Advances on Small-Molecule Antagonists Targeting TLR7.

Toll-like receptor 7 (TLR7) is a class of pattern recognition receptors (PRRs) recognizing the pathogen-associated elements and damage and as such is a major player in the innate immune system. TLR7 triggers the release of pro-inflammatory cytokines or type-I interferons (IFN), which is essential for immunoregulation. Increasing reports also highlight that the abnormal activation of endosomal TLR7 is implicated in various immune-related diseases, carcinogenesis as well as the proliferation of human immunodeficiency virus (HIV). Hence, the design and development of potent and selective TLR7 antagonists based on small molecules or oligonucleotides may offer new tools for the prevention and management of such diseases. In this review, we offer an updated overview of the main structural features and therapeutic potential of small-molecule antagonists of TLR7. Various heterocyclic scaffolds targeting TLR7 binding sites are presented: pyrazoloquinoxaline, quinazoline, purine, imidazopyridine, pyridone, benzanilide, pyrazolopyrimidine/pyridine, benzoxazole, indazole, indole, and quinoline. Additionally, their structure-activity relationships (SAR) studies associated with biological activities and protein binding modes are introduced.

[1,2,4]triazolo[4,3-a]quinoxaline as Novel Scaffold in the Imiqualines Family: Candidates with Cytotoxic Activities on Melanoma Cell Lines.

Cutaneous melanoma is one of the most aggressive human cancers and is the deadliest form of skin cancer, essentially due to metastases. Novel therapies are always required, since cutaneous melanoma develop resistance to oncogenic pathway inhibition treatment. The Imiqualine family is composed of heterocycles diversely substituted around imidazo[1,2-a]quinoxaline, imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline scaffolds, which display interesting activities on a panel of cancer cell lines, especially melanoma cell lines. We have designed and prepared novel compounds based on the [1,2,4]triazolo[4,3-a]quinoxaline scaffold through a common synthetic route, using 1-chloro-2-hydrazinoquinoxaline and an appropriate aldehyde. Cyclization is ensured by an oxidation-reduction mechanism using chloranil. The substituents on positions 1 and 8 were chosen based on previous structure-activity relationship (SAR) studies conducted within our heterocyclic Imiqualine family. Physicochemical parameters of all compounds have also been predicted. A375 melanoma cell line viability has been evaluated for 16 compounds. Among them, three novel [1,2,4]triazolo[4,3-a]quinoxalines display cytotoxic activities. Compounds 16a and 16b demonstrate relative activities in the micromolar range (respectively, 3158 nM and 3527 nM). Compound 17a shows the best EC50 of the novel series (365 nM), even if EAPB02303 remains the lead of the entire Imiqualine family (3 nM).

Apparent Absence of Selective Pressure on Pneumocystis jirovecii Organisms in Patients with Prior Methotrexate Exposure.

Pneumocystis jirovecii infections occur in patients treated with methotrexate (MTX) because of immunosuppressive effects of this highly potent dihydrofolate reductase (DHFR) inhibitor. Conversely, MTX may act as an anti-P. jirovecii drug and consequently may exert a selective pressure on this fungus. In this context, we compared the sequences of the dhfr gene of P. jirovecii isolates obtained from two groups of patients with P. jirovecii infections. The first group, with systemic diseases or malignancies, had prior exposure to MTX (21 patients), whereas the second group (22 patients), the control group, did not. Three single nucleotide polymorphisms (SNPs) were observed at positions 278, 312, and 381. The first one was located in the intronic region and the two others were synonymous. Based on these SNPs, three P. jirovecii dhfr alleles, named A, B, and C, were specified. Allele A was the most frequent, as it was observed in 18 patients (85.7%) and in 16 patients (72.7%) of the first and second groups, respectively. No significant difference in P. jirovecii dhfr gene diversity in the two patient groups was observed. In conclusion, these original results suggest that MTX does not exert an overt selective pressure on P. jirovecii organisms.

Highly Conserved gsc1 Gene of Pneumocystis jirovecii in Patients with or without Prior Exposure to Echinocandins.

Echinocandins are noncompetitive inhibitors of the GSC1 subunit of the enzymatic complex involved in synthesis of 1,3-beta-d-glucan, a cell wall component of most fungi, including Pneumocystis spp. Echinocandins are widely used for treating systemic candidiasis and rarely used for treating Pneumocystis pneumonia. Consequently, data on P. jirovecii gsc1 gene diversity are still scarce compared to that for the homologous fks1 gene of Candida spp. In this study, we analyzed P. jirovecii gsc1 gene diversity and the putative selection pressure of echinocandins on P. jirovecii. gsc1 gene sequences of P. jirovecii specimens from two patient groups were compared. One group of 27 patients had prior exposure to echinocandins, whereas the second group of 24 patients did not, at the time of P. jirovecii infection diagnoses. Two portions of the P. jirovecii gsc1 gene, HS1 and HS2, homologous to hot spots described in Candida spp., were sequenced. Three single-nucleotide polymorphisms (SNPs) at positions 2204, 2243, and 2303 close to the HS1 region and another SNP at position 4540 more distant from the HS2 region were identified. These SNPs represent synonymous mutations. Three gsc1 HS1 alleles, A, B, and C, and two gsc1 HS2 alleles, a and b, and four haplotypes, Ca, Cb, Aa, and Ba, were defined, without significant difference in haplotype distribution in both patient groups (P = 0.57). Considering the identical diversity of P. jirovecii gsc1 gene and the detection of synonymous mutations in both patient groups, no selection pressure of echinocandins among P. jirovecii microorganisms can be pointed out so far.

Convolutional neural networks improve species distribution modelling by capturing the spatial structure of the environment.

Convolutional Neural Networks (CNNs) are statistical models suited for learning complex visual patterns. In the context of Species Distribution Models (SDM) and in line with predictions of landscape ecology and island biogeography, CNN could grasp how local landscape structure affects prediction of species occurrence in SDMs. The prediction can thus reflect the signatures of entangled ecological processes. Although previous machine-learning based SDMs can learn complex influences of environmental predictors, they cannot acknowledge the influence of environmental structure in local landscapes (hence denoted "punctual models"). In this study, we applied CNNs to a large dataset of plant occurrences in France (GBIF), on a large taxonomical scale, to predict ranked relative probability of species (by joint learning) to any geographical position. We examined the way local environmental landscapes improve prediction by performing alternative CNN models deprived of information on landscape heterogeneity and structure ("ablation experiments"). We found that the landscape structure around location crucially contributed to improve predictive performance of CNN-SDMs. CNN models can classify the predicted distributions of many species, as other joint modelling approaches, but they further prove efficient in identifying the influence of local environmental landscapes. CNN can then represent signatures of spatially structured environmental drivers. The prediction gain is noticeable for rare species, which open promising perspectives for biodiversity monitoring and conservation strategies. Therefore, the approach is of both theoretical and practical interest. We discuss the way to test hypotheses on the patterns learnt by CNN, which should be essential for further interpretation of the ecological processes at play.

Domain Decomposition Spectral Method Applied to Modal Method: Direct and Inverse Spectral Transforms.

We introduce a Domain Decomposition Spectral Method (DDSM) as a solution for Maxwell's equations in the frequency domain. It will be illustrated in the framework of the Aperiodic Fourier Modal Method (AFMM). This method may be applied to compute the electromagnetic field diffracted by a large-scale surface under any kind of incident excitation. In the proposed approach, a large-size surface is decomposed into square sub-cells, and a projector, linking the set of eigenvectors of the large-scale problem to those of the small-size sub-cells, is defined. This projector allows one to associate univocally the spectrum of any electromagnetic field of a problem stated on the large-size domain with its footprint on the small-scale problem eigenfunctions. This approach is suitable for parallel computing, since the spectrum of the electromagnetic field is computed on each sub-cell independently from the others. In order to demonstrate the method's ability, to simulate both near and far fields of a full three-dimensional (3D) structure, we apply it to design large area diffractive metalenses with a conventional personal computer.

EAPB0503, an Imidazoquinoxaline Derivative Modulates SENP3/ARF Mediated SUMOylation, and Induces NPM1c Degradation in NPM1 Mutant AML.

Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML.

Diagnosis and treatment of pudendal and inferior cluneal nerve entrapment syndrome: a narrative review.

AIM: Pudendal and inferior cluneal nerve entrapment can cause a neuropathic pain syndrome in the sensitive areas innervated by these nerves. Diagnosis is challenging and patients often suffer several years before diagnosis is made. The purpose of the review was to inform healthcare workers about this disease and to provide a basis of anatomy and physiopathology, to inform about diagnostic tools and invasive or non-invasive treatment modalities and outcome. METHODS: A description of pudendal and inferior cluneal nerve anatomy is given. Physiopathology for entrapment is explained. Diagnostic criteria are described, and all non-invasive and invasive treatment options are discussed. RESULTS: The Nantes criteria offer a solid basis for diagnosing this rare condition. Treatment should be offered in a pluri-disciplinary setting and consists of avoidance of painful stimuli, physiotherapy, psychotherapy, pharmacological treatment led by tricyclic antidepressants and anticonvulsants. Nerve blocks are efficient at short term and serve mainly as a diagnostic tool. Pulsed radiofrequency (PRF) is described as a successful treatment option for pudendal neuralgia in patients non-responding to non-invasive treatment. If all other treatments fail, surgery can be offered. Different surgical procedures exist but only the open transgluteal approach has proven its efficacy compared to medical treatment. The minimal-invasive ENTRAMI technique offers the possibility to combine nerve release with pudendal neuromodulation. CONCLUSIONS: Pudendal and inferior cluneal nerve entrapment syndrome are a challenge not only for diagnosis but also for treatment. Different non-invasive and invasive treatment options exist and should be offered in a pluri-disciplinary setting.

The shift from pulmonary colonization to Pneumocystis pneumonia.

Pulmonary specimen pairs from five patients who presented with pulmonary colonization and later developed Pneumocystis Pneumonia (PcP) were retrospectively examined for P. jirovecii genotyping. A match of genotypes in pulmonary specimen pairs of three patients was observed, whereas a partial match and a mismatch were observed in the fourth and fifth patients, respectively. The genotyping results suggest that the colonization state can differ from PcP but can also represent the incubation period of PcP. Clinicians should not systematically rule out the treatment of putative colonized patients and should at least discuss the initiation of prophylaxis on a case-by-case basis.

The results suggest that clinicians should not systematically rule out the treatment of putative patients colonized by Pneumocystis jirovecii and should at least discuss prophylaxis initiation on a case-by-case basis.

Pilot study: pudendal neuromodulation combined with pudendal nerve release in case of chronic perineal pain syndrome. The ENTRAMI technique: early results.

INTRODUCTION AND HYPOTHESIS: Chronic perineal pain syndrome due to pudendal nerve impingement is difficult to diagnose and to treat. All the known treatment options leave room for improvement considering the outcome. Early neuromodulation of the pudendal nerve after its surgical release could improve outcomes. OBJECTIVES: The aim of the study was to evaluate the potential beneficial effect of pudendal neuromodulation combined with release surgery using the ENTRAMI technique (endoscopic transgluteal minimally invasive technique). STUDY DESIGN: This is a single-center prospective descriptive study. Between March 2019 and March 2020, 16 patients (2 males, 14 females) were included. Data were collected at baseline and 1 month after surgery. METHODS: Patients eligible for inclusion had chronic perineal pain for at least 3 months in the area served by the pudendal nerve. We combined pudendal nerve release with neuromodulation. RESULTS: At 1 month, the numeric pain rating scale (NPRS) dropped from 9.5 at baseline to 3.5 (p = 0.003). Seventy-six percent of patients showed a global impression of change (PGIC) of > 50% at 1 month, and optimal treatment response (PGIC ≥ 90%) was found in 41% of patients. LIMITATIONS: The drawback of our study was that it was not randomized or blinded. The peripheral nerve evaluation lead (PNE) used could only be implanted for 1 month because of infection risk and is also prone to dislocations and technical failures. CONCLUSION: Pudendal nerve liberation by the ENTRAMI technique combined with short-term pudendal neuromodulation seems feasible and promising in treating patients with chronic perineal pain. Clinical trial number: NCT03880786.

Parastomal hernia after radical cystectomy with ileal conduit diversion: a narrative review.

Radical cystectomy (RC) with ileal conduit urinary diversion has become a common surgical procedure. Stomal complications and particularly parastomal hernia (PH) are the most frequent complications and causes of reintervention after RC with ileal conduit urinary diversion. PH is usually asymptomatic. When PH increases in size and becomes symptomatic, it clearly impairs patients' quality of life in terms of physical limitation, mental distress and social interaction. The aim of this article was to review the current knowledge on PH after RC with ileal conduit urinary diversion, regarding its natural history, risk factors, prevention and surgical management. There is no strong recommendation on the ideal surgical technique for repair of PH after RC, but laparoscopic Sugarbaker or Sandwich techniques with non-absorbable meshes are emerging as the preferred modern means of PH repair. Techniques for prevention and repair of PH after RC need to be specifically evaluated in future prospective studies.

E-réputation : étude descriptive auprès de 240 médecins généralistes de région sud.

INTRODUCTION: E-reputation is the reputation of an entity on the Internet. This phenomenon lies within numerous domains, including the medical sector. The primary objective of this study was to describe the general practitioners' interest for their e-reputation and the e-reputation data available in the PACA region. The secondary objectives were to identify the determinants of the doctors' interest and feeling of control of their e-reputation. METHODS: The study was descriptive. The final sample was made of 240 physicians chosen randomly.The data collection has been done with a self-administered questionnaire and with a direct data collection on the Internet. RESULTS: The questionnaire answer rate was 64,2%. 51,3% of respondent physicians had no interest for their e-reputation, 9,7% had a strong or very strong interest. Physicians established for less than 25 years and physicians aged under 50 had more interest. 79,9% of respondent physicians considered to have no control of their online reputation (median value = 1). 71,6% out of the 240 interrogated physicians had at least one evaluation. The average number of evaluation per physician was 3,65 (standard deviation = 3,92). Physicians aged over 50 and physicians practising in urban area received a higher number of evaluations. 44,8% of physicians would like to be further informed on the way to answer opinions on the Internet. DISCUSSION: The physician's interest for their e-reputation was low. Their control was weak. They are however impacted by this phenomenon and are asking for information.

Machine Learning Using Digitized Herbarium Specimens to Advance Phenological Research.

Machine learning (ML) has great potential to drive scientific discovery by harvesting data from images of herbarium specimens-preserved plant material curated in natural history collections-but ML techniques have only recently been applied to this rich resource. ML has particularly strong prospects for the study of plant phenological events such as growth and reproduction. As a major indicator of climate change, driver of ecological processes, and critical determinant of plant fitness, plant phenology is an important frontier for the application of ML techniques for science and society. In the present article, we describe a generalized, modular ML workflow for extracting phenological data from images of herbarium specimens, and we discuss the advantages, limitations, and potential future improvements of this workflow. Strategic research and investment in specimen-based ML methods, along with the aggregation of herbarium specimen data, may give rise to a better understanding of life on Earth.

Synthesis of NiF2 and NiF2·4H2O Nanoparticles by Microemulsion and Their Self-Assembly.

Superstructures or self-assembled nanoparticles open the development of new materials with improved and/or novel properties. Here, we present nickel fluoride (NiF2) self-assemblies by successive preparatory methods. Originally, the self-assemblies were obtained by exploiting the water-in-oil microemulsion technique as a result of auto-organization of hydrated NiF2 (NiF2·4H2O) nanoparticles. The nanostructuration of NiF2·4H2O nanoparticles was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM) data. The size and shape of NiF2·4H2O nanoparticles and their subsequent self-assemblies varied slightly as a function of water-to-surfactant and water-to-oil ratios. Scanning electron microscopy (SEM) and TEM characterizations revealed that the nanoparticles are organized into a succession of self-assemblies: from individual nanoparticles assembled into layers to truncated bipyramids, which further auto-organized themselves into almond-shaped superstructures. Anhydrous NiF2 was achieved by heating NiF2·4H2O self-assemblies under the dynamic flow of molecular fluorine (F2) at a moderate temperature (350 °C). Preservation of self-assemblies during the transformation from NiF2·4H2O to NiF2 is successfully achieved. The obtained materials have a specific surface area (SSA) of about 30 m2/g, more than 60% of that of bulk NiF2. The lithium-ion (Li+) storage capacities and the mechanism of the nanostructured samples were tested and compared with the bulk material by galvanostatic cycling and X-ray absorption spectroscopy (XAS). The nanostructured samples show higher capacities (∼650 mAh/g) than the theoretical (554 mAh/g) first discharge capacity due to the concomitant redox conversion mechanism of NiF2 and solid-electrolyte interphase (SEI) formation. The nanostructuration by self-assembly appears to positively influence the lithium diffusion in comparison to the bulk material. Finally, the magnetic properties of nanostructured NiF2·xH2O (x = 0 or 4) have been measured and appear to be very similar to those of the corresponding bulk materials, without any visible size reduction effect. The hydrated samples NiF2·4H2O show an antiferromagnetic ordering at TN = 3.8 K, whereas the dehydrated ones (NiF2) present a canted antiferromagnetic ordering at TN = 74 K.

An in-line enzymatic microreactor for the middle-up analysis of monoclonal antibodies by capillary electrophoresis.

Monoclonal antibodies (mAbs) are undergoing rapid growth in the pharmaceutical industry due to their clinical efficiency. Concomitantly, robust, cost-effective, and high throughput analytical methods are needed for their quality control. Among all analytical techniques, capillary electrophoresis (CE) presents alternative and attractive features because the capillary can be used both as a microreactor and as a support for separation. Transverse diffusion of laminar flow profiles was applied for the middle-up analysis of mAbs for the first time. Infliximab was selected as the model mAb. All middle-up analysis steps (enzymatic digestion, electrophoretic separation and UV detection) were integrated into the same capillary. The conditions for the separation of infliximab subunits (pH, ionic strength, and type of background electrolyte) and in-line digestion parameters (reactant injection conditions, time, temperature and enzyme/mAb ratio) were optimized. The in-line methodology was compared to the off-line methodology and evaluated in terms of proteolysis efficiency, repeatability, and applicability to different mAbs. Finally, the methodology was transferred to capillary electrophoresis coupled to mass spectrometry (sheathless interface) to identify infliximab subunits. The in-line methodology was successfully implemented with a simplified injection scheme, temperature control, fast enzymatic reaction and high resolution of separation of infliximab subunits under pseudo-native MS compatible conditions. In comparison with the off-line methodology, reactant consumption was reduced by a factor of 1000, and the numbers of theoretical plates were increased by a factor of 2.

Endoscopic trans gluteal minimal-invasive approach for nerve liberation (ENTRAMI technique) in case of pudendal and/or cluneal neuralgia by entrapment: One-year follow-up.

BACKGROUND: Chronic neuropathic perineal pain syndrome is a collective term that encompasses several diagnoses. In patients where the neuropathic pain syndrome is caused by pudendal or cluneal nerve entrapment, surgical release can be proposed if other measures have failed. The aim of this study is to evaluate the clinical outcome of patients suffering from pudendal and/or cluneal nerve entrapment at 1 year after this minimal invasive surgery, which is based on the open trans gluteal approach who has proven its efficacy compared to medical treatment in a randomized control trial. METHODS: Patients eligible for inclusion had chronic perineal neuropathic pain for at least 3 months in the area served by the pudendal and/or cluneal nerve, refractory to conservative measurements. Patients met all five of the Nantes criteria. RESULTS: Fifteen patients underwent the ENTRAMI technique. At 1 year after surgery, overall reduction of the average maximal Numeric Pain rating Scale (NPRS-score) was from 9 (range, 7-10) at baseline to 5 (range, 0-10; P-value <.05). At 1 year 73% of patients declared to have a "good treatment response" (patient global impression of change [PGIC] >30%) and optimal treatment response (PGIC ≥90%) was found in 40% (P-value <.05). No complications were recorded. CONCLUSION: This study clearly shows that the technique is feasible with promising long-term results in a difficult to manage patient group.

Substantial Cellular Penetration of Fluorescent Imidazoquinoxalines.

Fluorescent tools have revolutionized our capability to visualize, probe, study, and understand the biological cellular properties, processes and dynamics, enabling researchers to improve their knowledge for example in cancer field. In this paper, we use the peculiar properties of our Imiqualines derivatives to study their cellular penetration and distribution in a human melanoma cell line A375 using confocal microscopy. Preliminary results on colocalization with the potent protein target c-Kit of our lead are also described.