Localization of interleukin-6 signaling complex in epithelialized apical lesions of endodontic origin.

OBJECTIVES: We aimed to determine the immunolocalization patterns of the interleukin (IL)-6 signaling complex in epithelialized and non-epithelialized apical lesions of endodontic origin (ALEOs). MATERIALS AND METHODS: Epithelialized (n = 8) and non-epithelialized (n = 7) ALEOs were obtained from teeth with indication of extraction in patients with clinical diagnosis of apical periodontitis. All tissues were subjected to routine processing for histopathologic examination and primary antibodies for IL-6, IL-6 receptor (R), and glycoprotein (gp)-130 were used for immunohistochemistry and double immunofluorescence co-localization. RESULTS: IL-6, IL-6R, and gp-130 were immunolocalized in endothelial cells and mononuclear leukocytes in a diffuse pattern within the connective tissue of epithelialized and non-epithelialized ALEOs. In the epithelialized lesions, two different patterns were identified: IL-6 signaling complex was localized within the proliferating epithelium in a diffuse intracellular pattern and in a cell membrane localization pattern within the mature epithelial lining, showing a decreased intensity towards the surface layers. CONCLUSIONS: IL-6, IL-6R, and gp-130 localized to mononuclear inflammatory cells, vascular endothelial cells, and immature proliferating epithelia in a diffuse pattern and in mature lining epithelia in a localized cell membrane pattern, supporting a role for epithelial proliferation during cyst formation. Additional cell membrane co-localization of IL-6 receptor complex suggests classic signaling involvement in addition to trans-signaling.

Management of obstructive sleep apnea syndrome type 1 in children and adolescents - A French consensus.

This document is the outcome of a group of experts brought together at the request of the French Society of Sleep Research and Medicine to provide recommendations for the management of obstructive sleep apnea syndrome type 1 (OSA1) in children. The recommendations are based on shared experience and published literature. OSA1 is suspected when several nighttime respiratory symptoms related to upper airway obstruction are identified on clinical history taking. A specialist otolaryngologist examination, including nasofibroscopy, is essential during diagnosis. A sleep study for OSA1 is not mandatory when at least two nighttime symptoms (including snoring) are noted. Therapeutic management must be individualized according to the location of the obstruction. Ear, nose, and throat (ENT) surgery is often required, as hypertrophy of the lymphoid tissues is the main cause of OSA1 in children. According to clinical findings, orthodontic treatment generally associated with specialized orofacial-myofunctional therapy might also be indicated. Whatever treatment is chosen, follow-up must be continuous and multidisciplinary, in a network of trained specialists.

Stimulus response latency of cough and expiration reflex depends on breathing in the rabbit.

Expiration reflex and cough may have distinct afferent pathways and/or central integrative mechanisms that may both result in different stimulus response latencies. A newly described method that uses a punctuate mechanical tracheal stimulus to provoke defensive ventilatory reflexes should allow the stimulus response latency to be calculated with reasonable accuracy. The aim of the study was to test whether cough and expiration reflex have different stimulus response latencies. Four hundred and sixty one mechanical tracheal stimulations (50-300 msec) were performed in 21 anesthetized, tracheotomized rabbits. Twenty three percent stimulations (108) provoked a cough reflex and 37% an expiration reflex (171). The individual mean stimulus response latency was computed for each reflex, calculated from stimulus onset to earliest detectable change in ventilatory flow. Cough reflex latency was significantly shorter in inspiration compared to expiration (257±19 msec vs 391±61 msec; p=0.01). In contrast, the expiration reflex latency was significantly shorter in expiration compared to inspiration (210±11 msec vs 329±29 msec, p=0.003). It is concluded that the within breath dependence of the difference in stimulus response latency between cough and expiration reflex is more likely to express different brainstem mechanisms but difference in afferent fibres may not be excluded.

Feedback regulation of the MBF transcription factor by cyclin Cig2.

The Mlu1-binding factor (MBF) from the fission yeast Schizosaccharomyces pombe contains the proteins Res1p and Res2p and binds to the Mlu1 cell-cycle box (MCB) element in DNA, activating the transcription of genes required for S phase. We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. Deletion of MCB elements in the cig2 promoter perturbed the expression not only of cig2 but also of other MBF-dependent genes, indicating that Cig2p could regulate MBF activity. Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle.

Assessment of antibiotic prescriptions in pediatric care units in a regional university hospital.

OBJECTIVES: The main objective was to assess the relevance of antibiotic prescriptions in the pediatric wards of a regional university hospital in France. Secondary objectives were to assess adequacy of the dose, administration frequency, administration route, treatment duration, adaptation to bacteriological results, and treatment reevaluation. PATIENTS AND METHODS: We assessed antibiotic prescriptions in pediatric settings. We included all patients under 18 years of age hospitalized in a pediatric ward who received a computerized prescription for antibiotic treatment between June 1st and June 30th, 2018; 163 clinical cases for 157 patients were analyzed. Patients hospitalized in neonatology, pediatric intensive care unit, and onco-hematology wards were excluded. RESULTS: The rate of relevance was 71%. The rates of adequacy for the other criteria were 60% for the dose, 99% for the administration frequency, 98% for the administration route, 72% for treatment duration, 98% for treatment adaptation to microbiological results, and 100% for treatment revaluation. All criteria combined, the overall rate of adequacy was 28%. CONCLUSIONS: Effort should be made regarding doses and treatment durations. Areas for improvement have been suggested to the wards: standardized prescription protocols, pediatric prescription guide, training of residents, setting up of the operational team in pediatric wards and a second clinical evaluation.

How do the FIFA World Cup 2018 and the 2016 UEFA championships impact a pediatric emergency department?

INTRODUCTION: In France, soccer is the most popular sport, which today attracts a huge television audience with millions of spectators in the case of international competitions. During certain games with European top clubs, the attendance of adult emergencies is impacted. However, the impact of international soccer competitions on pediatric emergency department (PED) activity has not been evaluated. METHODS: We performed a retrospective analysis of attendance in the PED of a tertiary university hospital in Nancy (France) during the UEFA 2016 championship and the FIFA 2018 World Cup. Games were represented by 2.5-h blocks and the tournament period was compared with the same period in the previous year. RESULTS: Considering all games, we did not observe an impact of PED attendance. The admission rate was significantly lower during the final phase (11.1 patients per match vs. 13.9, P=0.037). We observed a decrease in consultations for trauma (4.9 vs. 6.7, P=0.006). The effects were higher during games involving the national French team, with a decrease in less severe admissions (P=0.034), attendance of older children (P=0.016), and the presence of the father as accompanying adult (P=0.002). During the two final matches, we observed a decrease of 14% in the total activity. CONCLUSION: We found significant differences in PED attendance during two international soccer tournaments. It would be interesting to study this effect in countries other than France or in countries with different sport habits.

Management of eosinophilic esophagitis in children according to atopic status: A retrospective cohort in northeast of France.

INTRODUCTION: Most children with eosinophilic esophagitis (EoE) are atopic, but the impact of atopy on the remission and development of EoE is still unclear. The aim of our study was to determine the impact of atopy on remission of EoE and to describe allergy tests and the choice of treatment for a cohort of EoE children in France. METHODS: All children diagnosed with EoE between January 2013 and June 2018 in the five pediatric centers in the northeast of France were included. Children were divided into two groups according to personal atopic disorders. Histological remission was defined on the basis of an eosinophilic count below 15 eosinophils per high-power field. RESULTS: Among the 49 children included, 38 (78%) were atopic. Allergy tests were performed for 45 children (92%). Rates of sensitization were similar in both groups: 64% had food sensitization and 64% had aeroallergen sensitization. The most commonly attempted first-line therapy was with proton pump inhibitors (63%), followed by swallowed topical steroids (STS) (18%). First-line therapy was not associated with atopic status (P=0.88). Atopic children had a nonsignificant tendency for a higher remission rate after STS (55% vs. 0%, P=0.24) and a higher global remission rate (54% vs. 33%, P=0.18) compared with non-atopic children. CONCLUSION: Allergy testing is relevant in the majority of children with EoE whether or not they have atopic disorders. Atopy seems to be associated with better response to STS. Further studies are needed to determine whether atopic status determines histological response.

In Vivo Documentation of Stimulus Velocity Tuning of Mechanically Induced Reflex Cough.

In order to clear airways and lungs defensive reflexes are provoked rather by the dynamic phase of mechanical stimulus. It is speculated that provocation of defensive response depends not only on stimulus duration but also on stimulus velocity. Fourteen adult rabbits were anaesthetized and tracheotomized. Mechanical stimulus was provoked by a mechanical probe introduced through the tracheotomy and rotated by a small electrical motor using a rotational velocity of 40 rpm/s and 20 rpm/s. Threshold, incidence and intensity of cough reflex (CR) were analyzed for each animal. Statistical comparisons between two velocities were performed using Friedman nonparametric test for repeated measurements. Results are median (25-75 %). The threshold of CR was significantly increased (p=0.005) from 350 ms (300-500 ms) to 550 ms (350-1150 ms) and the incidence of cough reflex was significantly reduced (p=0.002) from 50 % (19 50 %) to 0 % (0-25 %) when the rotational velocity of the mechanical probe was reduced by half. The findings of this study are of interest as they show that protective reflex cough, an important mechanism that allows clearing airways even during sleep or anesthesia, is tuned by mechanical stimulus velocity.

Social motivation affects the display of individual discrimination in young and adult Japanese quail (Coturnix japonica).

A simultaneous two-choice test was used to investigate discrimination between a familiar (F) and an unfamiliar conspecific (U) in Japanese quail, selected for high (HSR) or low (LSR) social reinstatement behavior (tendency to rejoin and stay close to conspecifics). Animals were 1-week unsexed and 6-week-old male quail. One-week-old LSR quail and 6-week-old male HSR quail displayed discrimination after 24 hr of pair contact (p < 0.05), and a tendency to discriminate (p < 0.10) was found in adult male LSR quail. After 1 week of pair contact, results were similar in LSR quail chicks, but no discrimination was evidenced in adult quail of either line. Therefore, Japanese quail are able to discriminate between a familiar cagemate and an unfamiliar conspecific after only 24 hr of pair contact. Moreover, this study reveals for the first time in this species that social motivation and age both influence the display of individual discrimination.

Neonatal low respiratory tract chlamydia trachomatis infection: Diagnostic and treatment management.

Maternal infection during pregnancy by Chlamydia trachomatis (Chlamydia t.) can result in neonatal interstitial lung disease. It remains difficult for physicians to establish this diagnosis and to select the best treatment, as there is no recommendation. In these two cases of neonatal low respiratory tract Chlamydia t. infection, we proposed successfully a diagnosis method based on Chlamydia t. determination by PCR, on any type of sampling, but more specifically on urinary and pharyngeal specimens; and a management based on oral antibiotic therapy, Josamycin 50mg/kg/day during 14 days which is commonly well accepted and not invasive.

Exceptional preservation of mid-Cretaceous marine arthropods and the evolution of novel forms via heterochrony.

Evolutionary origins of novel forms are often obscure because early and transitional fossils tend to be rare, poorly preserved, or lack proper phylogenetic contexts. We describe a new, exceptionally preserved enigmatic crab from the mid-Cretaceous of Colombia and the United States, whose completeness illuminates the early disparity of the group and the origins of novel forms. Its large and unprotected compound eyes, small fusiform body, and leg-like mouthparts suggest larval trait retention into adulthood via heterochronic development (pedomorphosis), while its large oar-like legs represent the earliest known adaptations in crabs for active swimming. Our phylogenetic analyses, including representatives of all major lineages of fossil and extant crabs, challenge conventional views of their evolution by revealing multiple convergent losses of a typical "crab-like" body plan since the Early Cretaceous. These parallel morphological transformations may be associated with repeated invasions of novel environments, including the pelagic/necto-benthic zone in this pedomorphic chimera crab.

Evaluation of the Vitek-2 extended-spectrum beta-lactamase test against non-duplicate strains of Enterobacteriaceae producing a broad diversity of well-characterised beta-lactamases.

The Vitek-2 extended-spectrum beta-lactamase (ESBL) test was assessed using a collection of 94 ESBL-positive and 71 ESBL-negative non-duplicate isolates of Enterobacteriaceae. These isolates produced a wide diversity of well-characterised beta-lactamases, including 61 different ESBLs, two class A carbapenemases and various species-specific beta-lactamases. ESBL detection was performed using (i) the conventional synergy test as recommended by the Comité de l'Antibiogramme de la Société Française de Microbiologie, (ii) the CLSI phenotypic confirmatory test for ESBLs, and (iii) the Vitek-2 ESBL test. For Escherichia coli and klebsiellae, the sensitivity/specificity values were 97.3%/96.9% for the synergy test, 91.8%/100% for the CLSI phenotypic confirmatory test, and 91.8%/100% for the Vitek-2 ESBL test. For other organisms, the sensitivity/specificity values were 100%/97.4% for the synergy test, 90.5%/100% for the CLSI phenotypic confirmatory test, and 90.5%/100% for the Vitek-2 ESBL test. The Vitek-2 ESBL test seemed to be an efficient method for routine detection of ESBL-producing isolates of Enterobacteriaceae, including isolates producing AmpC-type enzymes.

Iodine deficiency, more than cretinism and goiter.

Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.

A dp/dt method to assess dynamic properties of lung mechanoreceptors.

The activity of airway slowly adapting mechanoreceptors (SARs) reflects the presence of both a static and dynamic component. The dynamic response is typically assessed by the adaptation index; however, this is an indirect reflection of the more appropriate physiological stimulus, the rate of change of inflation pressure (dp/dt). We describe a method in which measurement of receptor discharge exceeding the SAR static response is used to measure dynamic discharge and dynamic sensitivity of lung mechanoreceptors. Repeat inflations with varying dp/dt illustrate the method for a SAR in which the dynamic sensitivity is inversely related to dp/dt and the initial "onset" discharge is highly dp/dt sensitive. The method may provide new insight into the classification and behaviour of lung mechanoreceptors.