Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Efficacy and follow-up of anti-VEGF injections in diabetic macular edema in real-life practice at the Dijon university medical centre through the Save Sight Registries.

PURPOSE: To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (IVT) in diabetic macular edema (DME) in real-life practice using the Save Sight Registries (SSR). MATERIAL AND METHODS: We conducted an observational, single-centre, retrospective study in the department of ophthalmology of the Dijon University Hospital. We included treatment-naive patients who presented with DME between January 2016 and December 2017. Demographic and clinical data, follow-up visits, and treatments administered were entered into the SSR, an international online ophthalmic registry. Primary endpoints were the change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 12 and 24 months. RESULTS: Fifty-eight eyes of 43 patients with a mean [standard deviation (SD)] age of 67.1 [9.5] years were included. Forty-one eyes completed 12 months of follow-up, and 17 eyes completed 24 months of follow up. Median [SD] baseline BCVA was 56.1 [22.9] ETDRS letters and the median [95% confidence interval (95% CI)] baseline CST was 447.9 [161.0] micrometers (µm). Median [95% CI] improvement in BCVA from baseline to months 12 and 24 were respectively, +5.6 [+0.5; +10.7] ETDRS letters and +7.7 [-2.8; +18.2] ETDRS letters. The median [95% CI] decrease in CST from baseline to months 12 and 24 were respectively, -110.9 [-154.5; -67.3] µm and -125.5 [-198.0; -53.0] µm. CONCLUSION: Our clinical practice can be evaluated easily with the SSR system. In real life, anti-VEGF IVT are an effective treatment for DME, which result in improved BCVA and decreased CST.

Amlodipine-induced gingival enlargement: A case report.

Gingival enlargements (GEs) can be caused by local, systemic diseases or drugs. Three molecules can be responsible of GEs: ciclosporin, phenytoin and calcium channel blockers (CCBs). We report the case of a 56-year-old male treated by Amlodipine, a CCB, for hypertension for many years and who recently developed a severe GE affecting both mandibular and maxillary arches inducing dental malposition. The histological examination showed non-specific inflammation with a predominance of lymphocytes. Amlodipine was suspected and suspended in agreement with his physician. One month later, the enlargement significantly reduced but GE was so severe and dental malposition so marked that all the teeth but the canines were extracted. No recurrence was noted one year later. This exceptional case should encourage every practitioner to be vigilant with patient treated with CCBs and their potential side effects and consequences.

A new polymer-based approach for in vivo transfection in postnatal brain.

BACKGROUND: Gene delivery within the central nervous system at postnatal age is one of the most challenging tasks in neuroscience and currently only a few effective methods are available. COMPARISON WITH EXISTING METHODS: For postnatal central nervous system cells, viral approaches are commonly used for genetic engineering but they face several biosafety requirements for production and use making them less accessible to the community. Conversely, lipid-based methods are widely used in cell culture but face limitation in vivo mainly due to the inflammatory responses they induce. To this aspect, the use of a transgenic mouse line can represent a credible answer to the community working on rat models still requires an effective and successful solution to circumvent these difficulties. NEW METHOD: We describe a new polymer-based gene delivery system allowing persistent and robust in vivo transfection with low DNA amount, reduced inflammation and high diffusion. The expression profile along the brain, the stability, the diffusion of the DNA together with the quantity of cells transfected were evaluated through in vivo approaches. RESULTS: With a single low-volume injection, we targeted different cell types within the rat brain. We measured the diffusion rate ranging from 1 to 5 mm based on the injected volume, in the three-dimensions axis. Finally, we modified brain susceptibility to epileptic seizures using a specific knock-down of the neuronal specific potassium-chloride transporter 2. CONCLUSIONS: This safe and easy system opens perspectives for non viral gene delivery in the rat brain with perspectives to study brain function in vivo.

Morphology-induced phonon spectra of CdSe/CdS nanoplatelets: core/shell vs. core-crown.

Recently developed two-dimensional colloidal semiconductor nanocrystals, or nanoplatelets (NPLs), extend the palette of solution-processable free-standing 2D nanomaterials of high performance. Growing CdSe and CdS parts subsequently in either side-by-side or stacked manner results in core-crown or core/shell structures, respectively. Both kinds of heterogeneous NPLs find efficient applications and represent interesting materials to study the electronic and lattice excitations and interaction between them under strong one-directional confinement. Here, we investigated by Raman and infrared spectroscopy the phonon spectra and electron-phonon coupling in CdSe/CdS core/shell and core-crown NPLs. A number of distinct spectral features of the two NPL morphologies are observed, which are further modified by tuning the laser excitation energy Eexc between in- and off-resonant conditions. The general difference is the larger number of phonon modes in core/shell NPLs and their spectral shifts with increasing shell thickness, as well as with Eexc. This behaviour is explained by strong mutual influence of the core and shell and formation of combined phonon modes. In the core-crown structure, the CdSe and CdS modes preserve more independent behaviour with only interface modes forming the phonon overtones with phonons of the core.

EFS Centre-Atlantique donor's biobank: Ten years of samples usage.

INTRODUCTION: The French Establishment of Blood Centre Atlantique (EFSCA) is one of the French regional blood transfusion centers. Donor's biobank is a mandatory activity leading to the storage of biological samples taken from the blood donor. Samples of each blood donation are preserved for a 5-year period at Châteauroux in the form of two straws of 500microliters stored in liquid nitrogen. The aim of this study was to analyze the samples usage by studying quantitative, qualitative and economic criteria. MATERIAL AND METHOD: We analyzed all the requests of stored blood samples from 2005 to 2014. They were coming either from the blood donor qualification laboratory (BDQL), in order to perform complementary tests, or from hemovigilance inquiry. RESULTS: Among the blood donation samples, 2,144,636 (whole blood, plasma or platelets apheresis) were preserved during these ten years. During this period, 548 (0.025%) requests for samples were received; 78% were in relation with a request of the BDQL and 22% in relation with a request of hemovigilance. For the straws, the mean exit delay with regard to the blood donation date was 11.5 months (2-55). The cost of samples exit includes only working hours of a laboratory technician. On average, the annual working time dedicated to this activity was 23h. Also, the average price for one-year issuing activity was 620.31 euros. CONCLUSION: In our study, the donor's biobank was little used. The part of hemovigilance was weak but essential for the blood safety.

[CLOVES syndrome: a malformational syndrome closely resembling Proteus syndrome]. / Syndrome CLOVES: un syndrome malformatif proche du syndrome de Protée.

BACKGROUND: CLOVES syndrome (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal nevi, Skeletal anomalies) is a sporadic malformational syndrome that has recently been described (mutation of PIK3CA), with asymmetric body hypertrophy, lipomatous hamartoma of the trunk and numerous malformations. PATIENTS AND METHODS: We report a case of CLOVES syndrome initially diagnosed as Proteus syndrome, revealed by infection of a dorsal lipomatous hamartoma. The patient presented with both right lower limb hypertrophy and capillary and venous-lymphatic malformations, associated with dorsal capillary malformations, left cervico-facial hypertrophy, and cervical epidermal hamartoma, all of which are consistent with Proteus syndrome. Imaging of the dorsal lipomatous hamartoma associated with capillary as well as underlying venous-lymphatic malformations and syringomyelia resulted in subsequent correction of the earlier diagnosis of Proteus syndrome to that of CLOVES syndrome. DISCUSSION: Several malformational syndromes are associated with tissue hypertrophy, hamartoma and vascular malformations. Diagnosis of CLOVES syndrome may be delayed due to its fairly close phenotypic similarity to Proteus syndrome. Nevertheless, the prognosis and complications differ. Our case underlines the importance of considering a diagnosis of CLOVES syndrome in the presence of lipomatous hamartoma with hemi-hypertrophy and epidermal hamartoma, in order to enable adequate follow-up with specific monitoring for the possible complications associated with this disease.

Spectroscopy of colloidal semiconductor core/shell nanoplatelets with high quantum yield.

Free standing two-dimensional materials appear as a novel class of structures. Recently, the first colloidal two-dimensional heterostructures have been synthesized. These core/shell nanoplatelets are the first step toward colloidal quantum wells. Here, we study in detail the spectroscopic properties of this novel generation of colloidal nanoparticles. We show that core/shell CdSe/CdZnS nanoplatelets with 80% quantum yield can be obtained. The emission time trace of single core/shell nanoplatelets exhibits reduced blinking compared to core nanoplatelets with a two level emission time trace. At cryogenic temperatures, these nanoplatelets have a quantum yield close to 100% and a stable emission time trace. A solution of core/shell nanoplatelets has emission spectra with a full width half-maximum close to 20 nm, a value much lower than corresponding spherical or rod-shaped heterostructures. Using single particle spectroscopy, we show that the broadening of the emission spectra upon the shell deposition is not due to dispersity between particles but is related to an intrinsic increased exciton-phonon coupling in the shell. We also demonstrate that optical spectroscopy is a relevant tool to investigate the presence of traps induced by shell deposition. The spectroscopic properties of the core/shell nanoplatelets presented here strongly suggest that this new generation of objects will be an interesting alternative to spherical or rod-shaped nanocrystals.

Colloidal nanoplatelets with two-dimensional electronic structure.

The syntheses of strongly anisotropic nanocrystals with one dimension much smaller than the two others, such as nanoplatelets, are still greatly underdeveloped. Here, we demonstrate the formation of atomically flat quasi-two-dimensional colloidal CdSe, CdS and CdTe nanoplatelets with well-defined thicknesses ranging from 4 to 11 monolayers. These nanoplatelets have the electronic properties of two-dimensional quantum wells formed by molecular beam epitaxy, and their thickness-dependent absorption and emission spectra are described very well within an eight-band Pidgeon-Brown model. They present an extremely narrow emission spectrum with full-width at half-maximum less than 40 meV at room temperature. The radiative fluorescent lifetime measured in CdSe nanoplatelets decreases with temperature, reaching 1 ns at 6 K, two orders of magnitude less than for spherical CdSe nanoparticles. This makes the nanoplatelets the fastest colloidal fluorescent emitters and strongly suggests that they show a giant oscillator strength transition.

[Pyodermatitis-pyostomatitis vegetans with nasal involvement]. / Pyostomatite-pyodermatite végétante avec atteinte nasale.

BACKGROUND: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare chronic disorder often associated with inflammatory bowel disease. We report an isolated case involving the oral, labial and nasal mucosa. PATIENTS AND METHODS: A 28-year-old man, in good general condition, presented with a 2-year history of painless stomatitis. The physical examination revealed pustular and exophytic lesions of the jugal, gingival and palatine mucosa on an erythematous background, as well as some pustular and crusted lesions of the lower lip and nostrils. Histopathological analysis revealed epithelial hyperplasia and a suprabasal cleft with some signs of acantholysis and numerous neutrophils and eosinophils. Direct and indirect immunofluorescence assay was negative. There was no associated bowel disease. We concluded on a diagnosis of PPV of younger subjects. The lesions disappeared with oral corticosteroids but with steroid dependency. DISCUSSION: PPV is a rare dermatosis associated in more than 75% of cases with inflammatory bowel disease, usually ulcerative colitis. Lesions of the oral mucosa are a constant finding and are characterised by aseptic pustules on an erythematous background. Skin lesions are pustular and more or less exophytic. To our knowledge, there have been no reports to date of intranasal lesions of PPV.

[Gingival lichen planus]. / Le lichen plan gingival.

Lichen planus (LP) is a chronic inflammatory disease of uncertain etiology. When the gingiva is affected, the LP can appear under several clinical forms. The diagnosis of the gingival lichen planus is based on the anamnesis, the clinical observation and the histological analysis. Various medicamentous and non medicamentous treatments are used to treat gingival LP with random results, due to the lack of knowledge on the etiology and the recidiving character of the lesions. The risk of malignant transformation of gingival LP is weak but it depends on clinical forms, justifying a periodic follow-up of all patients.

[Desquamative gingivitis]. / La gingivite desquamative.

The desquamative gingivitis is the clinical term given to the gingival manifestation of mucocutaneous diseases. It is characterized by an erythematous, glazed, friable and hemorrhagic gingiva, which can be accompanied by pains. Except the gingiva, the lesions can be localised on other oral mucous membranes or on the skin. The three principal diseases at the origin of the desquamative gingivitis are by order of frequency: the cicatricial pemphigoïd, erosive lichen planus and pemphigus. The knowledge of the clinical, histological and immunohistochemical characteristics of these three affections is essential for the diagnosis and the suitable treatment of the desquamative gingivitis.

Lack of association of type 1 diabetes with the IL4R gene.

AIMS/HYPOTHESIS: The association between IL4R and type 1 diabetes has been tested in many studies in recent years, with contradictory results. The aim of this study was to re-evaluate the genetic association in type 1 diabetic nuclear families of mixed European background. SUBJECTS, MATERIALS AND METHODS: We genotyped six non-synonymous single-nucleotide polymorphisms (SNPs) of the IL4R gene in 830 nuclear families as specified above, including a French Canadian subset. RESULTS: No association between type 1 diabetes and any SNP or haplotype was found by the transmission disequilibrium test. CONCLUSIONS/INTERPRETATION: Previous positive reports may be due to population stratification as, according to HapMap data, allele frequencies in the IL4R region vary considerably by ethnicity.

Type 1 diabetes and the OAS gene cluster: association with splicing polymorphism or haplotype?

BACKGROUND: The 2',5'-oligoadenylate synthetase genes (OAS1, OAS2, and OAS3) map to human chromosome 12q24 and encode a family of enzymes pivotal to innate antiviral defence. Recently, the minor allele of an OAS1 single nucleotide polymorphism (SNP) that alters splicing (rs10774671) was found to be associated with increased enzymatic activity and, in a case-sibling control study, with type 1 diabetes (T1D). METHODS: We have confirmed this T1D association in 784 nuclear families (two parents and at least one affected offspring) by the transmission disequilibrium test (TDT; G:A = 386:329, p = 0.033). However, because of linkage disequilibrium within OAS1 and with the other two OAS genes, functional attribution of the association to this SNP cannot be assumed. To help answer this question, we also genotyped two non-synonymous SNPs in OAS1 exons 3 and 7. RESULTS: All three SNPs showed significant transmission distortion. Three of the eight possible haplotypes accounted for 98.4% of parental chromosomes and two of them carried the non-predisposing A allele at rs10774671. Parents heterozygous for these two haplotypes showed significant transmission distortion (p = 0.009) despite being homozygous at rs10774671. CONCLUSIONS: We confirm the T1D association with rs10774671, but we conclude that it cannot be attributed (solely) to the splicing variant rs10774671. A serine/glycine substitution in OAS1 exon 3 is more likely a functional variant.

Expression and analysis of the Epstein-Barr virus BARF1-encoded protein from a tetracycline-regulatable adenovirus system.

Epstein-Barr virus (EBV) has been associated with human cancers of lymphocytic or epithelial origin. Potential functions of the BARF1 early gene in EBV oncogenesis emerged from our observations showing expression of BARF1-encoded protein in nasopharyngeal carcinoma biopsies, and induction of either malignant transformation (in rodent fibroblast and human B cell lines) or immortalization (in monkey primary epithelial cells) following BARF1 transfection. We previously reported expression of the BARF1 product as a cytoplasm/membrane-associated protein from 293-tTA cells infected with a BARF1-recombinant adenovirus. Since constitutive expression of BARF1 from this heterologous system became inefficient, we developed a tetracycline-regulatable recombinant vector expressing BARF1 and green fluorescent protein from a dicistronic message. As here reported, stable and efficient expression of BARF1 from this vector in either permissive or non-permissive cell lines, allowed the first sequencing identification and further molecular characterization of BARF1-encoded protein.