Migraine treatment: Position paper of the French Headache Society.

The French migraine management recommendations were published in 2021. However, in the last three years, new data have come to light and new drugs have been approved (eptinezumab, rimegepant and atogepant) by the European Medicines Agency that require us to take a position on their use and to update certain elements of the recommendations. The first important message concerns the position of the French Headache Society on the use of preventive treatments (monoclonal antibodies and gepants) targeting the calcitonin gene-related peptide (CGRP) pathway. In terms of efficacy and safety, and as suggested by other national headache societies, these treatments can be offered as first-line treatment, although the scope defined by the French national health authority for possible reimbursement is limited to patients with severe migraine, at least eight headache days per month and for whom two previous preventive treatments have failed. Another important change concerns the position of topiramate as a preventive treatment for migraine in women of childbearing age. This treatment has been proposed as a first-line treatment for chronic migraine. However, recent pharmacovigilance data have highlighted a potential adverse effect on neurodevelopment in children exposed in utero. As a result, this treatment is formally contraindicated during pregnancy and must be used with extreme caution in women of childbearing age (effective contraception, no therapeutic alternative available and annual follow-up as with valproate). It can therefore no longer be offered as first-line treatment for women of childbearing age.

Immigration and adolescent health: the case of a multicultural population.

OBJECTIVES: Previous research indicates that the impact of immigration on health tends to be specific as it is influenced by many factors such as life stage and host country. The aim of this study was to examine the relationship between immigration and adolescent health within the multicultural context of the Brussels-Capital Region in Belgium. STUDY DESIGN: The study was based on the 2014 Health Behaviour in School-aged Children survey. The sample consisted of 2962 adolescents from the fifth grade of primary to the last grade of secondary schools in Brussels. METHODS: Associations between health indicators and immigration status were analysed using multivariable logistic regression models adjusted for sociodemographic characteristics. RESULTS: Natives, first-generation immigrants, second-generation immigrants with both parents born abroad and second-generation immigrants with one parent born abroad represented 19%, 23%, 36% and 22% of the respondents, respectively. Sociodemographic characteristics and health behaviours varied according to immigrant status. Young immigrants were more likely to present overweight (odds ratio [OR] first-generation immigrants vs. natives = 1.76 [95% confidence interval {CI} = 1.16-2.65]; OR second-generation immigrants with both parents born abroad vs. natives = 2.06 [95% CI = 1.41-3.02]; OR second-generation immigrants with one parent born abroad vs. natives = 1.69 [95% CI = 1.12-2.56]). This effect turned out to be partially explained by sociodemographic status and health-related behaviours. No association was detected between immigration and self-rated health and multiple recurrent symptoms. CONCLUSIONS: Discrepancies in health behaviours and weight status were identified between adolescents of different immigration background, whereas this was not the case for well-being. Socio-economic status, cultural characteristics and specific behaviours partly explained these findings. Future research is needed to better understand immigration-related risk and protective factors, at individual and school levels.

[Secondary facial recontouring with micro-porous titanium implants]. / Corrections secondaires de la face par implants en titane.

Facial recontouring has always been a longstanding objective of esthetic or reconstructive surgery. Most often it uses two types of surgical techniques: autologous and alloplastic. In that regard, different surgical techniques have been proposed to enhance facial recontouring. MATERIALS AND METHODS: Through 5 clinical case reports and a literature review, this article explores the use of allopastic microporous titanium implants in secondary volumetric corrections of the face. RESULTS: There is a current lack of evidence regarding the use of microporous titanium implants in volumetric corrections of the face, most papers reporting their use in post-traumatic or post-surgical cranio-facial defects repair. DISCUSSION: Pros and cons of such implants are discussed in association with the usefulness of this surgical technique in daily surgical practice.

Comparing impact on the family and insurance coverage in children with cerebral palsy and children with another special healthcare need.

BACKGROUND: Families and caregivers of children with special healthcare needs (CSHCN) often experience financial difficulties, have unmet physical and mental health needs, and are at increased risk of marital problems due to the stress caused by carrying for their child. Within the larger population of CHSCN, young people with cerebral palsy (CP) have more unmet needs due to the complexity and potential severity of the disability. The purpose of this study was to identify factors associated with differences in insurance coverage and impact on the family of children with CP and other CHSCN. METHODS: The data were taken from the National Survey of Children with Special Health Care Needs, which was designed to examine state- and national-level estimates of CSHCN. Three variables examined differences in insurance coverage between those children diagnosed with CP versus all other CSHCN: insurance coverage for the previous year, current insurance coverage, and adequacy of insurance coverage. Four variables representing different indicators of family impact were used to assess differences between children with CP versus all other CSHCN: out-of-pocket expenses for healthcare, family financial burden, hours per week that family members spent caring for the child, and impact on family work life. RESULTS: The results of this study showed significant differences between households with a child with CP and a child with another health special need in terms of insurance coverage, indicating a tendency of children with CP to be insured the entire year. As for the impact on the family in households with children with CP versus other CSHCN, there were significant differences in all four variables that were analysed. CONCLUSIONS: There is limited evidence highlighting differences between the impact of caring for a child with CP and caring for other CSHCN. Caring for a child with CP has a significant impact on the family, despite insurance coverage.

Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients.

WHAT IS KNOWN AND OBJECTIVE: The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. METHODS: This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. RESULTS AND DISCUSSION: Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). WHAT IS NEW AND CONCLUSION: Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients.

Upstream modes and antidots poison graphene quantum Hall effect.

The quantum Hall effect is the seminal example of topological protection, as charge carriers are transmitted through one-dimensional edge channels where backscattering is prohibited. Graphene has made its marks as an exceptional platform to reveal new facets of this remarkable property. However, in conventional Hall bar geometries, topological protection of graphene edge channels is found regrettably less robust than in high mobility semi-conductors. Here, we explore graphene quantum Hall regime at the local scale, using a scanning gate microscope. We reveal the detrimental influence of antidots along the graphene edges, mediating backscattering towards upstream edge channels, hence triggering topological breakdown. Combined with simulations, our experimental results provide further insights into graphene quantum Hall channels vulnerability. In turn, this may ease future developments towards precise manipulation of topologically protected edge channels hosted in various types of two-dimensional crystals.

Association of nucleoplasmin with transcription products as revealed by immunolocalization in the amphibian oocyte.

The oocyte nucleus of Pleurodeles waltlii contains a major 32,000-mol-wt acidic protein which is called nucleoplasmin. Rabbit antibodies were raised against total nuclear proteins from Pleurodeles oocytes. Affinity-purified antibodies directed against nucleoplasmin were prepared using antigens bound to nitrocellulose paper. The specificity of the antibody was controlled on two-dimensional electrophoretic gels of nuclear proteins. The intranuclear distribution of nucleoplasmin was analyzed by indirect immunofluorescence and the immunogold technique in light and electron microscopy. The antibody was tested on a spread of the nuclear content prepared in the presence of calcium, on the nuclear content spread in the presence of phalloidin so that an actin network appeared, and on a spread of nuclei from oocytes previously treated by actinomycin D. In all cases, nucleoplasmin appeared to be localized on the lampbrush loops, i.e., on the sites of transcription and, more specifically, on the ribonucleoprotein (RNP) particles; this protein was also associated with the RNP particles of the nuclear sap (free or inserted in the actin network). Nucleoplasmin was localized on large RNP particles that appeared when transcription was blocked. We never found this protein on the chromosome axis. These results suggest that nucleoplasmin may play a role in transcriptional activity.

A rare ectopic localization of pleomorphic adenoma.

INTRODUCTION: Pleomorphic adenoma (PA) is the most common benign salivary gland tumor, frequently affecting the major salivary glands but also the palatal or labial minor salivary glands. Pleomorphic adenomas affecting the retromolar trigone have seldom been reported with only few cases described in the literature. OBSERVATION: We present the case of a young female patient who presented with this rare localization of pleomorphic adenoma and its subsequent management. DISCUSSION: Pleomorphic adenoma of the retromolar trigone is a rare occurrence. Nevertheless, when faced with a swelling of the retromolar trigone, a diagnosis of pleomorphic adenoma should not be omitted from the differential.

Selection of anionic exchange resins for removal of natural organic matter (NOM) fractions.

Early elimination of natural organic matter (NOM) by ion exchange (IEX) in water treatment is expected to improve subsequent water treatment processes and the final drinking water quality. Nine anionic exchange resins were investigated to remove NOM and specific NOM fractions determined by liquid chromatography in combination with organic carbon detection (LC-OCD) and fluorescence excitation-emission matrices (EEM). Breakthrough of NOM was predicted by model calculations using Freundlich isotherms and IEX rate experiments. The time to breakthrough varied from 4 to 38 days. Removal of specific NOM fractions proved to vary considerably for the different types of IEX resins, ranging from 1% to almost 60%. The removal of NOM fractions, specifically humic substances, increased with an increase in water content of the investigated IEX resins and with a decrease in resin size. The best-performing IEX resins consisted of the smallest resins and/or those with the highest water content. The worst-performing IEX resins reflected the highest exchanging capacities and the lowest water contents.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

INTRODUCTION: Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. METHODS: The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. RESULTS: 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. CONCLUSION: These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development.

Hedgehog Pathway-Mediated Vascular Alterations Following Trigeminal Nerve Injury.

Whereas neurovascular interactions in spinal neuropathic pain models have been well characterized, little attention has been given to such neurovascular interactions in orofacial neuropathic pain models. This study investigated in male Sprague-Dawley rats the vascular changes following chronic constriction injury (CCI) of the infraorbital nerve (IoN), a broadly validated preclinical model of orofacial neuropathic pain. Following IoN-CCI, an early downregulation of tight junction proteins Claudin-1 and Claudin-5 was observed within the endoneurium and perineurium, associated with increased local accumulation of sodium fluorescein (NaFlu) within the IoN parenchyma, as compared with sham animals. These events were evidence of local blood-nerve barrier disruption and increased vascular permeability. A significant upregulation of immunocytes (CD3, CD11b) and innate immunity (TLR2, TLR4) mRNA markers was also observed, suggestive of increased local inflammation. Finally, a significant downregulation of Hedgehog pathway readouts Patched-1 and Gli-1 was observed within the IoN after CCI and local injections of cyclopamine, a Hedgehog pathway inhibitor, replicated in naïve rats the molecular, vascular, and behavioral changes observed following IoN-CCI. These results suggest a major role of Hedgehog pathway inhibition in mediating local increased endoneurial and perineurial vascular permeability following trigeminal nerve injury, thus facilitating immunocytes infiltration, neuroinflammation development, and neuropathic pain-like aversive behavior.

Immunolocalization of HSP 70-related proteins constitutively expressed during Xenopus laevis oogenesis and development.

Using immunocytochemical and biochemical methods, we analyzed the localization of HSP 70-related proteins constitutively expressed during oogenesis and embryogenesis in the amphibian Xenopus laevis. Our results provided evidence for a regional localization in oocytes. In embryos, the regional distribution observed in oocytes was found to be maintained from fertilization up to late blastula. It is noteworthy that, at the beginning of gastrulation, nuclear transfer of such proteins had already occurred by the time of internalization in the involuting marginal zone (IMZ), whereas cells of the vegetal area exhibited only a perinuclear localization of these proteins. These results suggest that HSP 70-related proteins might be involved in the control of the process of cellular internalization.

Cell-cycle-dependent nuclear translocation of HSP70 in amphibian embryonic cells.

Using immunocytochemical methods, we analyzed the localization of the HSP70 protein constitutively expressed during embryogenesis in the amphibian Pleurodeles waltl. Our results provide evidence for nuclear transfer of the protein during gastrulation, and particularly for predominant nuclear labeling in gastrula internalized cells. Using two inhibitors of DNA replication -hydroxyurea (HUA) and aphidicolin- or/and an inhibitor of transcription -actinomycin D- applied to embryos, we demonstrated that nuclear transfer of HSP70 is related to the transcriptional activity of the cells during the early S phase of the cell cycle.

Does the chaperone heat shock protein hsp70 play a role in the control of developmental processes?

Expression of an hsp70 gene strictly inducible in somatic cells and constitutively expressed during oogenesis was investigated during embryogenesis of the amphibian Pleurodeles waltl. Results from Northern hybridization experiments and RNase protection assays provided evidence for the presence of inducible hsp70 mRNA under normal conditions at every embryonic stage. Immunoblotting of embryo proteins separated by 2D-electrophoresis provided evidence for the presence of a single polypeptide of about 74 kDa likely to be an HSP70-related protein, from unfertilized egg to tailbud stage. Immunocytological analysis showed that HSP70-related proteins were localized in the cytoplasm of all blastomeres. It also pointed out that nuclear transfer of the protein occurs in certain cells, precisely at the time of their invagination and subsequent internalization during normal Pleurodeles development. Such nuclear transfer involves involuting mesodermal cells in the blastopore region at the time of gastrulation. It also involves neurodermic cells at the time of neural tube closure. Interestingly, in exogastrulas nuclear transfer did not occur in cells which could no longer invaginate. Such behavior of HSP70-related proteins led us to suggest that they are involved in the control of nuclear activity associated with important developmental events such as cellular internalization processes. Such a role may be a direct consequence of HSP70-related protein functional properties as molecular chaperones.

NUDC expression during amphibian development.

To identify gene products important for gastrulation in the amphibian Pleurodeles waltl, a screen for regional differences in new protein expression at the early gastrula stage was performed. A 45 kDa protein whose synthesis was specific for progenitor endodermal cells was identified. Microsequencing and cDNA cloning showed that P45 is highly homologous to rat NUDC, a protein suggested to play a role in nuclear migration. Although PNUDC can be detected in all regions of the embryo, its de novo synthesis is tightly regulated spatially and temporally throughout oogenesis and embryonic development. New PNUDC synthesis in the progenitor endodermal cells depends on induction by the mesodermal cells in the gastrula. During development, PNUDC is localized in the egg cortical cytoplasm, at the cleavage furrow during the first embryonic division, around the nuclei and cortical regions of bottle cells in the gastrula, and at the basal region of polarized tissues in the developing embryo. These results show for the first time the expression and compartmentalization of PNUDC at distinct stages during amphibian development.

Chromosomes of amphibian oocytes as a model for gene expression: significance of lampbrush loops.

Amphibian lampbrush chromosome loops exhibit morphological variability in their RNP matrix. The biological significance of such variability remains unknown. In order to approach this problem, the structural organization of each RNP matrix type was analyzed in relation to transcriptional and post-transcriptional processes. First, autoradiographic and transcription inhibition studies in conjunction with macromolecular spread analysis revealed a particular transcription pattern in the most typical loops, i.e. the globular loops. This pattern was characterized by asynchronous variations in RNA synthesis in the different transcription units present in a given loop. Second, morphological and experimental studies provided evidence that the typical morphologies of different RNP matrices were interconvertible and that the differences between the different RNP matrices resulted from various degrees of tightness in packaging of transcription products. In particular, analysis of thermic-shock-induced changes in the structure of lampbrush chromosomes enabled us to visualize the progressive disorganization of dense RNP matrices into globular, granular and normal matrices. Furthermore, these studies suggested that changes in post-transcriptional processes might play a determining role in the specific morphology of the loops. In particular, the kinetics of each of these different processes, related to one another and/or proteins specific to one or another of these processes, might determine the morphological appearance of the loops. The immunological approach revealed that specific nuclear proteins might therefore interfere with each of these processes. Third, the problem of a possible relationship between the specific morphologies of lateral loops and the expression of particular DNA sequences was approached at the molecular level.

[Purification of the bacterial ribosome using chloramphenicol and erythromycin columns]. / Purification du ribosome bactérien à l'aide de colonnes de chloramphénicol et d'érythromycine.

Chloramphenicol and erythromycin are antibiotics whose target is the bacterial ribosome. We have studied the possibility of isolating the bacterial ribosome by affinity chromatography on chloramphenicol and erythromycin columns. Several columns have been prepared using different spacers and methods of attachment of the ligands (cyanogen bromide, bis-expoxyde). The efficiency and specificity of these columns is discussed. Ethylene diamine is not always suitable as a spacer, because it presents non specific affinity for the ribosome. Pure tight ribosomes have been prepared by ultracentrifugation. They have been compared to ribosomes from affinity columns. These columns have no denaturing effect on ribosomes. They allow a good purification of ribosomes starting from crude bacterial extracts, but the separation of tight couples from loose subunits is not possible.

Synthesis and activities of pyoverdin-quinolone adducts: a prospective approach to a specific Therapy against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of (55)Fe using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with P. aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is labile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.