Dental and extra-oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype-phenotype study.

WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. In patients, WNT10A mutations are responsible for ectodermal-derived pathologies including isolated hypo-oligodontia, tricho-odonto-onycho-dermal dysplasia and Schöpf-Schulz-Passarge syndrome (SSPS). Here we describe the dental, ectodermal, and extra-ectodermal phenotypic features of a cohort of 41 patients from 32 unrelated families. Correlations with WNT10A molecular status (heterozygous carrier, compound heterozygous, homozygous) and patient's phenotypes were performed. Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. However, patients with compound heterozygous mutations presented no significant difference in phenotypes compared with homozygous individuals. Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. No signs of SSPS, especially eyelids cysts, were detected in our cohort. Interestingly, extra-ectodermal signs consisted of skeletal, neurological and vascular anomalies, the latter suggesting a wider phenotypic spectrum associated with WNT10A mutations. Indeed, the Wnt pathway plays a crucial role in skeletal development, lipid metabolism, and neurogenesis, potentially explaining patient's clinical manifestations.

Prospective cohort study of phenotypic variation based on an anal sphincter function in adults with fecal incontinence.

BACKGROUND: One-third of patients with fecal incontinence (FI) do not have any anal dysfunction. The aim was to characterize patients with FI with normal anal function compared with patients with anal weakness. METHODS: The general characteristics and data of anal manometry, endosonography, and defecography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by the Cleveland Clinic Incontinence Score (CCIS) >4. Anal weakness was defined by one or more of the three following parameters: <25 mmHg at the upper part of the anal canal, <26 mmHg at the lower part of the anal canal, and <60 mmHg for the mean squeeze pressure. KEY RESULTS: A total of 439 patients with FI were included (152 with normal anal function/287 with anal weakness). Severe constipation (Kess score ≥21) was predominant in patients with normal anal function (44/151 vs 50/284, respectively; p = 0.0054). Fecal incontinence with normal anal function was significantly associated with lower age (>63 years; odds ratio [OR] = 0.29), higher weight (>65 kg; OR = 1.69), fecal urgency (OR = 1.58), less severe FI score (CCIS score >10; OR = 0.52), higher abdominal pressure (>36 mmHg; OR = 2.15), and paradoxical puborectal contraction (OR = 2.07) in a multivariate analysis model. CONCLUSION & INFERENCES: Fecal incontinence with normal anal function is a specific phenotype that involves distal constipation and may be an early stage of FI with anal weakness. Physicians should adapt their management to focus on the treatment of constipation.

A cross reactive sensor array to probe divalent metal ions.

A simple sensing ensemble was designed to discriminate structurally similar divalent metal chlorides utilizing multivariate data analysis. The system features the binding of four synthesized coumarin-enamine probes to a series of ten metal chlorides. Linear discriminant analysis (LDA) achieves what univariate data analysis alone cannot i.e., full analyte discrimination and differentiation.

[Effectiveness of flexible ureteroscopy versus extracorporeal shock wave lithotripsy for kidney stones treatment]. / Efficacité de l'urétéroscopie souple versus lithotritie extracorporelle dans le traitement des calculs du rein.

Primary endpoint was to objective a better effectiveness of flexible ureteroscopy (fURS) compared to extracorporeal shock wave lithotripsy (ESWL) 3 months after treatment of a unique kidney stone from 5 to 20mm. Secondary endpoints were to evaluate effectiveness in subgroup and tolerance. We conducted a prospective comparative randomised trial between May 2012 and February 2014. A computerised tomography was done before treatment and another 3 months after treatment. Of the 30 randomised patients, 8 dropped out from the study and 4 were lost to follow-up. Median time of follow-up was 3.82 months. In per-protocol analysis, success rate was 60% for fURS group versus 28.6% for ESWL group (P=0.29). In intention to treat analysis, success rate was 77.8% in fURS group versus 53.8% in ESWL group (P=0.38). In ESWL group, 5 patients (41.7%) needed a second treatment versus none in fURS group but it was not significant. During follow-up, 1 patient in each group presented a complication. Results of this feasibility study did not allowed to conclude on superiority of a technic. A multicenter study with more important enrollment is necessary considering economic side and tolerance of these treatments.

Why are head and neck squamous cell carcinoma diagnosed so late? Influence of health care disparities and socio-economic factors.

CONTEXT: Late stage diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) makes the prognosis worse. However, the influence of inequalities of health care and socio-economic factors has never been investigated in this pathology. OBJECTIVES: To identify any inequalities in health care and socio-economic factors influencing late-stage diagnosis of HSNCC. DESIGN: The ASED study (Acces aux Soins avant Endoscopie Diagnostique) was a cross-sectional observational, multi-centric (19 centers) study on metropolitan French territory. Data was collected from 1st December 2010 to 30th June 2012. SETTING: Patients were included prospectively in Head and Neck Surgery departments. A self-administered form was completed by the patients at the time of ambulatory diagnostic endoscopy (38 items describing demographic, socio-economic and health care access characteristics). A second form was completed by the surgeon at the time of histological confirmation of HNSCC (11 items describing the tumor). PATIENTS: Six hundred and ninety patients aged 18 or more with a first HNSCC were included. Exclusion criteria were second HSNCC or loco-regional recurrence of HNSCC. MAIN OUTCOME MEASURE(S): Late-stage was defined as T3/T4 tumor, and early-stage was defined as T1/T2 tumor, according to the TNM classification. RESULTS: Independent factors associated with late-stage diagnosis were: hypopharyngeal location (OR=3.5 [1.8-7.3] versus oral cavity location), age (OR=1.02 [1.00-1.04]), male sex (OR=1.7 [1.1-2.6]) and being born in France (OR=2 [1.2-3.3]). Factors associated with early-stage diagnosis were previous consultation to a specialist physician (OR=0.5 [0.4-0.8]), ease of access to this specialist (OR=0.6 [0.4-0.9]), and having a health professional in close contact (OR=0.6 [0.4-0.8]). Time to consultation was identical in both groups. No significant association was found between socio-economic factors (especially deprivation or alcohol and tobacco consumption) and late-stage diagnosis of HNSCC. CONCLUSION: Health care access in France plays a major role in the stage of HNSCC at diagnosis. Easy access to a specialist protects from late-stage diagnosis. Absence of socio-economic factors may be due to the French social security system and its comprehensive coverage of the population.

Chemical characterization of the Allium sativum and Origanum vulgare essential oils and their inhibition effect on the growth of some food pathogens / Caracterização química e efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento de alguns patógenos de alimentos

This study sought to evaluate the chemical composition of the Allium sativum and Origanum vulgare essential oils and their effect on the growth inhibition of microorganisms, such as P. aeruginosa, S. Choleraesuis, A. flavus, A. niger and P. simplicissimum, important food contaminants. The main constituents of the oregano essential oil were 4-terpineol (27.03%), γ-terpinene (20.04%), and β-cymene (6.34%), and the main constituents of the garlic essential oil were diallyl trisulfide (38, 81%), diallyl disulfide (25.23%), and methyl allyl trisulfide (12.52%). Inhibition zones were formed in in vitro tests on the bacteria S. Choleraesuis and P. aeruginosa, except for A. sativum against P. aeruginosa. The inhibition of mycelial growth caused by the oregano essential oil occurred with the concentrations of 0.10, 0.03 and 0.05 mg mL-1 for the A. flavus, A. niger and P. simplicissimum fungi, respectively. The CMI for the garlic oil began at the 0.03 mg mL-1 concentration for all species of fungi. The oils presented an inhibitory effect against the microorganisms studied and constitute an alternative for microbiological control in food.

Objetivou-se avaliar a composição química e o efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento dos micro-organismos Pseudomonas aeruginosa, Salmonella Choleraesuis, Aspergillus flavus, Aspergillus niger e Penicillium simplicissimum, importantes patógenos causadores de contaminações em alimentos. Para quantificação e identificação dos constituintes químicos dos óleos, utilizou-se cromatógrafo gasoso acoplado a espectrômetro de massas. Os principais constituintes do óleo essencial de orégano foram o 4-terpineol (27,03%), γ-terpineno (20,04%), β-cimeno (6,34%), e do alho, o dialil trissulfeto (38,81%), dialil dissulfeto (25,23%), metil alil trissulfeto (12,52%). Os resultados dos testes in vitro sobre as bactérias S. Choleraesuis e P. aeruginosa indicaram a formação de halo de inibição e revelaram o efeito inibitório para os referidos óleos, exceto para o óleo de A. sativum frente a P. aeruginosa. Para os fungos A. flavus, A. niger e P. simplicissimum a inibição do crescimento micelial provocada pelo óleo essencial de orégano ocorreu a partir das concentrações de 0,10, 0,03 e 0,05 µg mL-1, respectivamente, sendo que a CMI para o óleo de alho iniciou-se a partir da concentração 0,03 µg mL-1 para todas as espécies de fungos. Foi possível verificar que os óleos possuem efeito inibitório sobre os microrganismos estudados, sendo, portanto, uma alternativa no controle microbiológico de alimentos.

Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.

BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN. METHODS: A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional.

Peptic ulcer disease: one in five is related to neither Helicobacter pylori nor aspirin/NSAID intake.

BACKGROUND: The proportion (and even the reality) of peptic ulcer disease (PUD) not related to H. pylori or NSAID/aspirin is debated. AIM: To analyse the current epidemiological and clinical characteristics of peptic ulcer disease in French general hospitals. METHODS: Prospective multicentre study of patients with peptic ulcer disease in 32 French general hospitals over 1 year. H. pylori status was assessed by histology, and/or serology and/or C13-urea breath test. NSAID/aspirin intake (obtained by direct interview) and data about concomitant diseases were collected on the day of endoscopy. RESULTS: Nine hundred and thirty-three patients were selected during the year 2009. After exclusion of 118 patients with only erosive duodenitis, 24 with major missing data, 13 with other causes of ulcer and 65 negative for H. pylori by only one test, 713 patients were classified into four groups: 285 (40.0%) had only H. pylori infection; 133 (18.7%) only gastrotoxic drugs; 141 (19.8%) had both and 154 (21.6%) neither H. pylori infection nor gastrotoxic drug intake ('idiopathic ulcers'). Patients with idiopathic ulcers differed in many ways both from H. pylori and NSAID/aspirin groups. However, multivariate analysis identified only three independent predictors: age, French metropolitan origin and the presence of comorbidities. CONCLUSION: In a general hospital-based population in France, peptic ulcer disease appears idiopathic in a fifth of cases.

[Appraisal of the optical diagnostic technique for cervical intra-epithelial neoplasia by polarimetric imaging "Polcolpo". Comparison with colposcopic and histological diagnoses by biopsy]. / Étude prospective comparant les performances de la colposcopie classique à la colposcopie guidée par polarimétrie sur la détection des néoplasies intra-épithéliales du col utérin.

OBJECTIVES: The main objective of this study was to compare the performances of polarimetric imaging and standard colposcopy for the detection of CIN. MATERIALS AND METHODS: We performed a monocentric prospective clinical study. The standard colposcopic diagnosis obtained during a first consultation was compared to the diagnosis provided by polarimetric imaging in a second consultation. In addition to the biopsies guided by classical or polarimetric colposcopy, a systematic biopsy taken at a predefined location allowed to calculate the specificities and sensitivities of both techniques. RESULTS: One hundred and forty-one patients were included, all of them with anomalous Pap smears. Sixty-seven cone biopsies were taken, 69 % of which were eventually diagnosed with CIN2+ lesions. The sensitivities and specificities were found to be equal for standard and polarimetric colposcopies. CONCLUSION: We could not demonstrate any improvement of the diagnostic performances with polarimetric colposcopy alone. However, for both healthy and pathological cervices, we observed interesting polarimetric responses involving other characteristics than those we initially assumed, and which will be taken into account in a future study.

Alignment and scaling of large-scale fluctuations in the solar wind.

We investigate the dependence of solar wind fluctuations measured by the Wind spacecraft on scale and on the degree of alignment between oppositely directed Elsasser fields. This alignment controls the strength of the nonlinear interactions and, therefore, the turbulence. We find that at scales larger than the outer scale of the turbulence the Elsasser fluctuations become on average more antialigned as the outer scale is approached from above. Conditioning structure functions using the alignment angle reveals turbulent scaling of unaligned fluctuations at scales previously believed to lie outside the turbulent cascade in the "1/f range." We argue that the 1/f range contains a mixture of a noninteracting antialigned population of Alfvén waves and magnetic force-free structures plus a subdominant population of unaligned cascading turbulent fluctuations.

Bone marrow oedema predicts structural progression in a 1-year follow-up of 85 patients with RA in remission or with low disease activity with low-field MRI.

OBJECTIVES: To identify the predictive factors of MRI-determined structural progression in patients with rheumatoid arthritis (RA) in remission or with low disease activity (LDA). METHODS: In this 1-year longitudinal study, patients with RA in clinical remission (disease activity score (DAS) 44≤1.6) or with LDA (1.6

Óleo essencial de Baccharis tridentata Vahl: composição química, atividade antioxidante e fungitóxica, e caracterização morfológica das estruturas secretoras por microscopia eletrônica de varredura / Baccharis tridentata Vahl essential oil: chemical composition, and antioxidant and fungitoxic activities and morphological characterization of secretory structures by scanning electron microscopy

Este trabalho teve como objetivos avaliar a composição química do óleo essencial de Baccharis tridentata Vahl, as atividades antioxidante e fungitóxica, e estudar a morfologia das estruturas secretoras do óleo essencial presentes na superfície foliar por meio de microscopia eletrônica de varredura (MEV). A extração do óleo essencial foi realizada por hidrodestilação, as análises quantitativas e qualitativas foram executadas por meio de cromatografia em fase gasosa com detector de ionização de chamas (FID) e acoplada à espectrometria de massas, respectivamente. A atividade antioxidante foi realizada empregando-se os métodos de redução do radical estável DPPH e o ensaio de oxidação do sistema β-caroteno/ácido linoleico. As atividades fungitóxicas foram avaliadas utilizando o teste bioanalítico in vitro, sobre a inibição do crescimento micelial dos fitopatógenos Fusarium oxysporum, Colletotrichum gloeosporioides e Rhizoctonia solani. A composição química revelou a presença de 28 compostos, sendo o α-tujeno (22,93 por cento) o constituinte majoritário; não foi observada atividade antioxidante por meio dos ensaios utilizados, no entanto, observou-se atividade fungitóxica sobre o crescimento micelial dos fitopatógenos estudados. Já os estudos da superfície foliar por MEV revelaram a presença de tricomas glandulares em ambas as superfícies abaxial e adaxial.

This study aimed to evaluate the chemical composition and the antioxidant and fungitoxic activities of Baccharis tridentata essential oil, as well as to study the morphology of its secretory structures present on the leaf surface by scanning electron microscopy (SEM). The essential oil was extracted by hydrodistillation; the quantitative and qualitative analyses were performed on a gas chromatograph equipped with a flame ionization detector (FID) and coupled to a mass spectrometer, respectively. The antioxidant activity was determined by the methods of reduction of the DPPH stable radical and oxidation of the β-carotene/linoleic acid system. Fungitoxic activities were assessed by the in vitro bioanalytical test on the inhibition of the mycelial growth of the plant pathogens Fusarium oxysporum, Colletotrichum gloeosporioides and Rhizoctonia solani. The chemical composition revealed the presence of 28 compounds, with α-thujene (22.93 percent) as the major constituent. No antioxidant activity was observed in the tests used; however, there was fungitoxic activity against the mycelial growth of plant pathogens. Leaf surface studies by SEM revealed the presence of glandular trichomes on both abaxial and adaxial surfaces.

A medical simulator for subcutaneous contraceptive implant insertion.

New contraceptive methods like the subcutaneous implant offers a new kind of comfort for women with an efficiency similar to the contraceptive pill. Unfortunately the few numbers of unintended pregnancies that have been reported are generally due to a bad insertion of the implant. In order to give more security to patients, we have designed, in close collaboration with physicians, a new kind of medical simulator. This paper focuses on a device dedicated to a specific subcutaneous implant but it is worth noting that this simulator is relatively generic since it will be used for other subcutaneous techniques or other implant instruments. This simulator can be used for two purposes: one for training novice physicians in the correct manipulation and the other for physician certification which will help determine if they are capable of inserting the implant in vivo. This paper describes the approach which has led to the design of this simulator. It describes its functionalities, its several components but also methods used to analyze the manipulation of the implant insertion inside the patient. Finally first experimental results are reported and discussed. The system used in this paper makes possible to carry out training in a constraint-free context and provides the first mean of visualizing a maneuver that, until now, has been performed blindly.

Evaluation of data quality in a laboratory-based surveillance of M. tuberculosis drug resistance and impact on the prevalence of resistance: France, 2004.

In France, surveillance of anti-tuberculosis drug resistance is performed by the Azay-Mycobacteria network, representing 30% of all culture-positive cases. We sought to validate administrative and clinical data gathered by the network in 2004 and to produce corrected resistance rates accounting for the observed misclassification. We reviewed a 10% sample of patients' records diagnosed in 2004 and measured the agreement between controlled data and data collected by the network by using the kappa (kappa) statistic. A re-sampling bootstrap-based method was used to investigate the impact of bias found on resistance rates. Most of data collected by the network, such as demographic data, and country of birth had an excellent agreement (kappa>0.8) with controlled data. The concordance was good (kappa>0.6) for HIV status and tuberculosis site. The only variable slightly discordant with controlled data was prior history of treatment (kappa=0.52). However, after correcting crude resistance rates for the observed misclassification, all estimated rates were within confidence intervals based on reported rates. This validation study is in favour of a good quality of data produced by the network, even though corrected rates are slightly different from observed rates. Therefore, data collected through the network may be used for policy making and tuberculosis programme evaluation. However, improvement in data collection regarding prior history of treatment should be considered.

Design of a medical simulator for subcutaneous contraceptive implant insertion.

New contraceptive methods like the subcutaneous implant offers a new kind of comfort for women with an efficiency similar to the contraceptive pill. Unfortunately, the few numbers of unintended pregnancies that have been reported, are generally due to a bad insertion of the implant. In order to give more security to patients, we have designed, in close collaboration with physicians, a new kind of medical simulator. This simulator can be used for two purposes: one for training novice physicians in the correct gesture and the other for doctor certification which will help to determine if they are capable of inserting the implant in vivo. This paper describes the approach which has led to the design of this simulator. It describes its functionalities, its several components but also methods used to analyze the gesture of the implant insertion inside the patient. Finally, first experimental results are reported and discussed.

Kinematic and electromyographic analysis of rising from a chair during a "Sit-to-Walk" task in elderly subjects: role of strength.

BACKGROUND: With aging, the deterioration of the ability to rise from a chair constitutes a major source of disability and a factor contributing to the loss of autonomy. The aim of this study was to describe kinematic and electromyographic characteristics of rising from a chair during a Sit-to-Walk task and to investigate the relationships between lower limb muscle strength and Sit-to-Walk characteristics. METHODS: Twenty-four healthy elderly subjects (mean age: 73.8 (6.4) years) were included. The task analyzed consisted in standing up and taking a step. Kinematic data were obtained using a 3D motion analysis software. Surface electromyography of eight lower limb muscles was recorded. Isokinetic strength of ankle plantar flexor and knee flexors and extensors was evaluated. FINDINGS: The Sit-to-Walk was divided into four phases. For 19 subjects, this task can be considered as a continuum with an overlap of the phases. In comparison with the Sit-to-Stand description, the Sit-to-Walk transition phase, which combined trunk flexion and knee extension, appeared longer in order to increase the body forward transfer for gait initiation. In most cases, the tibialis anterior and peroneus longus muscles were first activated. The isokinetic strength of the knee extensors was negatively correlated with the amplitude of trunk flexion and the knee flexors/extensors torque ratio was correlated with the length of this phase. INTERPRETATION: Characterization of Sit-to-Walk movement provides information about the ability to rise from a chair. In the elderly, a better knowledge of its determinants could lead to improve strategies for rehabilitation of this critical task.

Anemia in the period immediately following renal transplantation.

INTRODUCTION: Anemia remains frequent in the first month following renal transplantation and is a risk factor for cardiovascular accidents. The purpose of this study was to analyze the prevalence of anemia during this period notably among different immunosuppressive treatment groups. METHODS: In this study, we entered the patients who had received a renal allograft in our transplant unit from 1993 to 2003, including patients who had received azathioprine (AZA) from 1993 to 1996 and mycophenolate mofetil (MMF) from 1996 to 2003. No patient received rHu-erythropoietin after transplantation during that period. A mathematical model normalized the hemoglobin (Hb) threshold level at which blood transfusion was decided and Hb on admission. RESULTS: One hundred and eighty-eight patients on AZA and 223 on MMF were included in the analysis. The mean age +/- SD was 41 +/- 12 years in the AZA group, and 45 +/- 12 years in the MMF group (P < .006). Before the transplantation, Hb was higher in the MMF group (11.4 +/- 1.9 vs 10.2 +/- 2 g/dL, P < .0001). After normalization at a threshold level of transfusion of 7 g/dL, transfusions were more frequent among the MMF group (72% vs 48%, P < .0001). Double therapy with MMF (1500 mg/d) + steroids or therapy with MMF (750 mg/d) + tacrolimus + steroids increased the risk of transfusion compared to the AZA group. MMF (750 mg/d) + cyclosporine conferred a similar risk of transfusion compared with the AZA group. CONCLUSION: MMF alone or in association with tacrolimus is associated with an increased risk of anemia and transfusion in the immediate posttransplantation period.