Management of atopic dermatitis by pediatricians: A French national survey-based study.

PURPOSE: Atopic dermatitis (AD) is a chronic skin disease affecting 10% of children in Europe. The treatment of AD is well codified; however, a gap sometimes exists between recommendations and medical practice. The objective of this study was to assess the practice of French pediatricians regarding the management of AD. METHODS: We conducted a national practice survey from September 2021 to October 2021, using an online questionnaire emailed to pediatric physicians. RESULTS: A total of 83 pediatricians from 33 different departments responded to the survey. The clinical features of AD were known by the majority of pediatricians, but 15 (18%) found the diagnosis difficult to establish. All pediatricians prescribed daily applications of emollients and 78 (94%) prescribed topical corticosteroids (TCS) during AD flares, but misuses remained: only 29 (35%) pediatricians prescribed TCS when eczema (even if minimal) appeared and 43 (52%) did so at the onset of pruritus, while 45 (54%) prescribed them for extensive or disabling eczema, and 53 (64%) when eczema persisted after an initial treatment with emollients. Regarding diet, 12 (14%) pediatricians recommended a diet low on or free of cow milk, 10 (12%) systematically referred children with AD to an allergist, and 20 (24%) delayed food diversification. CONCLUSION: Despite improvements in AD management by French pediatricians in the past 15 years, barriers to its appropriate management still persist, including the misuse of TCS and inappropriate diets.

Drug-induced enterocolitis syndrome: A rare, severe, non-IgE-mediated immediate drug allergy. Case report and literature review.

We report the case of a 4-year-old child who presented with vomiting, abdominal pain, and intense pallor 2 h after amoxicillin ingestion. An IgE-mediated reaction was suspected at first, which was finally diagnosed as a drug-induced enterocolitis syndrome. In this rare and poorly described non-IgE-mediated drug allergy, adrenaline is not effective. This diagnostic challenge must be known in order to administer adequate treatment, i.e., antiemetic drugs (ondansetron) and fluid challenge.

Oral immunotherapy in food allergies: A practical update for pediatricians.

Food oral immunotherapy (OIT) is a promising treatment for persistent and severe food allergies (FAs) in children, but also for accelerating tolerance to cow's milk and cooked egg in young children. In the near future, pediatricians will increasingly encounter severely allergic children undergoing FA-OIT. FA-OIT consists in daily ingestion of increasing doses of the allergen during the up-dosing phase, and ingestion of a constant dose during the maintenance phase. The global aim is to increase the reactive threshold of allergic patients, and finally enable them to ingest a target quantity of allergen without any reaction throughout the treatment (desensitization). Many studies showed the efficacy of FA-OIT in desensitization, and some of them in sustained unresponsiveness. This corresponds to tolerance after FA-OIT discontinuation, especially for cow's milk and hen's egg allergy. However, there is an ongoing debate about the safety of the treatment. Side effects are frequent, notably aversion to the allergen and oral syndromes as well as systemic allergic symptoms. These reactions occur mainly during the up-dosing phase and become less frequent with time, but they are common causes of FA-OIT discontinuation. Patients and their families must be trained to manage these reactions at home. Long-term side effects can also occur, such as eosinophilic esophagitis. Pediatricians play an important role in maintaining patient motivation; they also provide knowledge on possible allergic reactions and the reactogenic cofactors (mainly fever and viral infection, anti-inflammatory intake, physical activity), and refer the patient to the relevant specialists in the case of long-term care. Other routes of administration for food immunotherapy (epicutaneous and sublingual) and different adjuvant treatments (probiotics, anti-IgE molecule) are currently under study. This will allow us to improve the efficacy of immunotherapy and reduce the risk of any side effects, in order to provide a more favorable risk-benefit ratio.

Physiopathologie de la dermatite atopique et des autres maladies atopiques : une approche globale est-elle possible ?: Pathophysiology of atopic dermatitis and other atopic diseases: is a global approach possible?

Atopy is defined by the propensity to develop an exaggerated type-2 inflammatory response to environmental molecules. Clinically, atopy is diagnosed when atopic disease occurs: atopic dermatitis, food allergy, atopic asthma and allergic rhinitis and conjunctivitis. Whereas the classical "atopic march" is increasingly challenged through epidemiological studies, type-2 cellular inflammation is a characteristic shared by the atopic diseases. This inflammation can be innate (non-specific: eosinophils, mast cells, dendritic cells, innate lymphoid cells [ILC]), or adaptive (antigen-specific, involving T cells). Interleukins (IL-)4, 5 and 13 are major actors of type-2 inflammation and are mainly produced by ILC and T cells. The efficacy of treatments targeting these type-2 cytokines highlight the importance of type-2 inflammation in atopic diseases. However, several patients do not respond to type-2 targeting treatments, highlighting the presence of other actors in pathophysiology of atopic diseases: alteration of epithelial barrier, IgE-mediated allergic responses, type-17 inflammation. Thus, the term "endotype" can illustrate this diversity in pathophysiology. Finally, a global approach of atopic diseases, as type-2 inflammatory diseases, is fundamental, but not sufficient. An approach by endotype is advisable, in a personalized medicine perspective. © 2020 Elsevier Masson SAS. All rights reserved.

In search of a dose-response relationship in SSRIs-a systematic review, meta-analysis, and network meta-analysis.

OBJECTIVE: Recent meta-analyses on dose-response relationships of SSRIs are largely based on indirect evidence. We analyzed RCTs directly comparing different SSRI doses. METHOD: Systematic literature search for RCTs. Two raters independently screened articles and extracted data. Across SSRIs, doses defined as low, medium, and high doses, based on drug manufacturers' product monographs, were analyzed in pairwise random-effects meta-analyses and in a sensitivity network meta-analysis with regard to differences in antidepressive efficacy (primary outcome). We also analyzed all direct comparisons of different dosages of specific SSRIs. (Prospero CRD42018081031). RESULTS: Out of 5333 articles screened, we included 33. Comparisons of dosage groups (low, medium, and high) resulted in only small and clinically non-significant differences for SSRIs as a group, the strongest relating to medium vs low doses (SMD: -0.15 [95%-CI: -0.28; -0.01) and not sustained in a sensitivity analysis. Among different doses of specific SSRIs, no statistically significant trend emerged for efficacy at higher doses, but 60 mg/day fluoxetine are statistically significantly inferior to 20 mg/day. Paroxetine results are inconclusive: 10 mg/day are inferior to higher doses, but 30 and 40 mg/day are inferior to 20 mg/day. Meaningful effects cannot be ruled out for certain drugs and dosages, often investigated in only one trial. Dropout rates increase with dose-particularly due to side effects. Network meta-analyses supported our findings. CONCLUSIONS: There is no conclusive level I or level II evidence of a clinically meaningful dose-response relationship of SSRIs as a group or of single substances. High SSRI doses are not recommended as routine treatment.

Vibration-Driven Self-Doping of Dangling-Bond Wires on Si(553)-Au Surfaces.

Density-functional theory is used to explore the Si(553)-Au surface dynamics. Our study (i) reveals a complex two-stage order-disorder phase transition where with rising temperature first the ×3 order along the Si step edges and, subsequently, the ×2 order of the Au chains is lost, (ii) identifies the transient modification of the electron chemical potential during soft Au chain vibrations as instrumental for disorder at the step edge, and (iii) shows that the transition leads to a self-doping of the Si dangling-bond wire at the step edge. The calculations are corroborated by Raman measurements of surface phonon modes and explain previous electron diffraction, scanning tunneling microscopy, and surface transport data.

Medical and gynecological comorbidities in adult women with Turner syndrome: our multidisciplinary clinic experience.

Objective: Women with Turner syndrome (TS) are at increased risk for chronic health conditions. Reports describing the presence of comorbidities in older adult women with TS are limited. This study aimed to examine the prevalence of endocrine, gynecological, and other chronic medical conditions in a cohort of adult TS patients.Methods: A retrospective chart review was conducted on patients seen between 1 February 2015 and 1 July 2018 in a multidisciplinary TS clinic at a university-based ambulatory hospital in Toronto, Canada. All women seen at the TS clinic with a diagnosis of TS aged >18 years were included. The prevalence of diseases was determined overall and stratified by age (<40 and ≥40 years). Statistical comparisons were done using the chi-square test. The main study outcomes included the presence of comorbidities.Results: Of 122 adult women with TS, 24.5% had hypothyroidism, 16% had dysglycemia, and 27.9% had decreased bone mass. Hypothyroidism and dysglycemia were more common among older women (respectively age ≥40 years vs. age <40 years: 36.7% vs. 17.8%, p = 0.018; and 24.5% vs. 5.5%, p = 0.023). Gynecological conditions were identified in 35% of patients and were more common among older women (42.8% age ≥40 years vs. 13.7% age <40 years, p = 0.003). Overall, 41% had hearing impairment, 36.1% had cardiac abnormalities, 14.8% had hypertension, 18.8% had renal abnormalities, and 9% had celiac disease.Conclusions: The results of this study indicate a high prevalence of medical conditions in women with TS, especially those ≥40 years of age. Our study underscores the importance of multidisciplinary adult TS clinics for ongoing screening and management of comorbidities.

Contrasting global, regional and local patterns of genetic structure in gray reef shark populations from the Indo-Pacific region.

Human activities have resulted in the loss of over 90% of sharks in most ocean basins and one in four species of elasmobranch are now listed at risk of extinction by the IUCN. How this collapse will affect the ability of populations to recover in the face of continued exploitation and global climate change remains unknown. Indeed, important ecological and biological information are lacking for most shark species, particularly estimates of genetic diversity and population structure over a range of spatial scales. Using 15 microsatellite markers, we investigated genetic diversity and population structure in gray reef sharks over their Indo-Pacific range (407 specimens from 9 localities). Clear genetic differentiation was observed between the Indian and the Pacific Ocean specimens (FST = 0.145***). Further differentiation within the Pacific included a West and East cleavage as well as North-Central and South-Central Pacific clusters. No genetic differentiation was detected within archipelagos. These results highlight the legacy of past climate changes and the effects of large ocean expanses and circulation patterns on contrasting levels of connectivity at global, regional and local scales. Our results indicate a need for regional conservation units for gray reef sharks and pinpoint the isolation and vulnerability of their French Polynesian population.

Inhibition in the somatosensory system: An integrative neuropharmacological and neuroimaging approach.

The presented study investigates the functional role of GABA in somatosensory processing, using a combined neuropharmacological-neuroimaging approach. Three different GABA agonists (GABAA: alprazolam, ethanol; GABAB: baclofen) were investigated in a double blind cross-over design in 16 male participants, accomplishing a tactile perception task. Somatosensory evoked magnetic fields modulated by GABAR-agonists and placebo were recorded using whole-head magnetoencephalography. Peak latencies and amplitudes of primary (SI) and secondary (SII) somatosensory cortex source activities confirmed the previously reported role of GABA as a modulator of somatosensory processing. Significant inhibitory effects on the latency of SII and on the amplitude of SI and SII were found exclusively for alprazolam, a positive allosteric modulator at GABAA receptors. The GABAB agonist baclofen did not have any modulatory effect. Moreover, we investigated whether the observed effects of alprazolam on the level of SII were explainable by the mere propagation of activity from SI to SII modulated by GABAA receptors, independently from any further GABAA-mediated inhibition in SII. By estimating the transfer function between SI and SII activation under placebo conditions, we were able to predict SII activity for the administration of GABA receptors agonists under the assumption that GABA exclusively acts at the level of SI. By comparing measured and predicted data, we propose a model in which the initial activation of SI is modulated through GABAA receptors and subsequently propagated to SII, without any significant further inhibition. In addition, initial GABAA effects in SI appear to be strongly potentiated with time, selectively in SI but not in SII.

Influence of reconstruction settings in electrical impedance tomography on figures of merit and physiological parameters.

OBJECTIVE: Electrical impedance tomography (EIT) is a non-invasive and relatively cheap imaging technique allowing continuous monitoring of lung function at the bedside. However, image reconstruction and processing are not yet standardized for clinical use, limiting comparability and reproducibility between studies. In addition, optimal reconstruction settings still have to be identified for different clinical applications. In this work (i) a systematic way to select 'good' EIT algorithm parameters is developed and (ii) an evaluation of these parameters in terms of correct functional imaging and consistency is performed. APPROACH: First, 19 200 reconstruction models are generated by full factorial design of experiment in 5D space. Then, in order to quantify the quality of reconstruction, known conductivity changes are introduced and figures of merit (FoM) are calculated from the response image. These measures are further used to select a subset of reconstruction models, matching certain FoM thresholds, and are then used for in vivo evaluation. For this purpose, EIT images of one piglet are reconstructed to assess changes in tidal impedance and end-expiratory lung impedance, at positive end expiratory pressure of 0 and 15 cmH2O. From ground truth spirometry measurements, physiological criteria are formulated and the subset of models is further reduced. Finally, the remaining reconstruction models are evaluated on physiological data gathered from published data in the literature to assess the generalization possibilities. MAIN RESULTS: Parametrization of EIT image reconstruction has a strong influence on the resulting FoM and the derived physiological parameter. While numerous reconstruction models showed reasonable values for a single parameter, in total only 12 matched all simulation and physiological criteria. After validation on further physiological data, only a single reconstruction model remained with a noise figure of 0.3, target size of 0.08, weight radius of 0.3, normalized voltage and strong weighting of lung and heart regions. Furthermore, the relationship between the reconstruction settings and some FoM could be partly explained by using a linear statistical model. SIGNIFICANCE: The quest for standard reconstruction settings is highly relevant for future clinical applications. Simulation measures might help to assess the quality of the reconstruction models, but further evaluation of more data and different experimental settings is required.

Histoire naturelle de la dermatite atopique: Natural History of Atopic Dermatitis.

Atopic dermatitis (AD) is a common frequent chronic inflammatory skin disease which begins frequently in infancy. The clinical expression of AD is a recurrent eczema on a dry skin. AD is a multifactorial disease characterized by two linked abnormalities: a skin barrier defect and a cellular inflammation, with type-2 main components. However, the pathophysiology of AD is not as simple as this description looks like. In this review, we will present a synthesis of current knowledge on natural history of AD and the involved factors, in order to clarify AD care. The evolution of AD is associated with many atopic comorbidities, following the "atopic march" scheme: IgE-mediated food allergy, allergic asthma and rhinitis occurring classically after AD. In fact, this is rarely the case, but the atopic march seems to be associated with AD severity. AD has also many neuropsychological complications which are essential to be detected. Other factors could influence the natural history of AD: genetic mutations on different genes (proteins of skin barrier, innate and adaptive immunity pathways), skin dysbiosis with colonization by Staphylococcus aureus, sensitization against environmental proteins. AD treatment is based on the restauration of the skin barrier using emollients and on anti-inflammatory drugs (notably topical corticosteroids) during the inflammatory flares. It is not recommended to treat the skin colonization by S. aureus, excepted in case of skin infection. The probiotics have no efficiency as curative treatment of AD, but could have an interest for the primary prevention, especially in at-risk populations. © 2019 Elsevier Masson SAS. All rights reserved.

Directional K+ channel insertion in a single phospholipid bilayer: Neutron reflectometry and electrophysiology in the joint exploration of a model membrane functional platform.

We investigated the insertion of small potassium (K+) channel proteins (KcvMA-1D and KcvNTS) into model membranes and the lipid-protein structural interference, combining neutron reflectometry and electrophysiology. Neutron reflectometry experiments showed how the transverse structure and mechanical properties of the bilayer were modified, upon insertion of the proteins in single model-membranes, either supported on solid substrate or floating. Parallel electrophysiology experiments were performed on the same channels reconstituted in free-standing planar lipid bilayers, of both typical composition and matched to the neutron reflectometry experiment, assessing their electrical features. Functional and structural results converge in detecting that the proteins, conical in shape, insert with a directionality, cytosolic side first. Our work addresses the powerful combination of the two experimental approaches. We show here that membrane structure spectroscopy and ion channel electrophysiology can become synergistic tools in the analysis of structural-functional properties of biomimetic complex environment.

Photon Subtraction by Many-Body Decoherence.

We experimentally and theoretically investigate the scattering of a photonic quantum field from another stored in a strongly interacting atomic Rydberg ensemble. Considering the many-body limit of this problem, we derive an exact solution to the scattering-induced spatial decoherence of multiple stored photons, allowing for a rigorous understanding of the underlying dissipative quantum dynamics. Combined with our experiments, this analysis reveals a correlated coherence-protection process in which the scattering from one excitation can shield all others from spatial decoherence. We discuss how this effect can be used to manipulate light at the quantum level, providing a robust mechanism for single-photon subtraction, and experimentally demonstrate this capability.

Convergence of marine megafauna movement patterns in coastal and open oceans.

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals' movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.

Clinical outcome after alternative treatment of scaphoid fractures and nonunions.

PURPOSE: Achieving stable fixation of scaphoid fractures and nonunions continues to be a challenge. Compression screw fixation has been the current standard surgical procedure. However, in some cases, bone healing cannot be achieved and requires further revision. Recent series reintroduced volar plating as valid option for stable fixation. The aim of the study was to review clinical outcome of alternative scaphoid treatment. METHODS: From 2011 to 2014, nine patients with scaphoid fracture were treated by Headless Compression Screw (HCS) and seven patients with scaphoid nonunion by HCS or volar mini condylar plate with bone graft. The average age was 34.4 years and the average time to follow-up was 19.3 months. From 1996 to 1998, 38 patients with scaphoid nonunion were treated using compression screw (S-group) or volar mini condylar plate (P-group) with bone graft. The average age was 39.6 years and the average time to follow-up was 26.2 months. RESULTS: The union rate was 100%. For scaphoid fractures, the mean Modified Mayo Wrist Score (MMWS) was 94.1 and the DASH score 7.4. From 2011 to 2014, the MMWS was 87.9 and the DASH score 7 in scaphoid nonunions. In the period between 1996 and 1998, the MMWS was 67.2 in the P-group and 58.6 in the S-group, and the DASH score 16.8 and 28.2. CONCLUSIONS: Our study demonstrated that appropriate application of the HCS was able to produce very satisfactory results in scaphoid fractures and nonunions. In our opinion, however, the method of scaphoid plate osteosynthesis can achieve a higher degree of stability, particularly rotational stability, in case of multifragmentary avascular scaphoid nonunions.

Resistance to Fluopicolide and Propamocarb and Baseline Sensitivity to Ethaboxam Among Isolates of Pseudoperonospora cubensis From the Eastern United States.

Chemical control is currently the most effective method for controlling cucurbit downy mildew (CDM) caused by Pseudoperonospora cubensis. Most commercial cucurbit cultivars, with the exception of a few new cucumber cultivars, lack adequate disease resistance. Fluopicolide and propamocarb were among the most effective fungicides against CDM in the United States between 2006 and 2009. Since then, reduced efficacy of these two fungicides under field conditions was reported starting around 2013 but occurrence of resistance to fluopicolide and propamocarb in field isolates of P. cubensis had not been established. Thirty-one isolates collected from cucurbits in the eastern United States were tested for their sensitivity to fluopicolide and propamocarb using a leaf disc assay. This same set of isolates and four additional isolates (i.e., 35 isolates) were also used to establish the baseline sensitivity of P. cubensis to ethaboxam, an ethylamino-thiazole-carboxamide fungicide, which was recently granted registration to control CDM in the United States. About 65% of the isolates tested were resistant to fluopicolide with at least one resistant isolate being present in samples collected from 12 of the 13 states in the eastern United States. About 74% of the isolates tested were sensitive to propamocarb with at least one resistant isolate being among samples collected from 8 of the 12 states in the study. The frequency of resistance to fluopicolide and propamocarb was high among isolates collected from cucumber, while the frequency was low among isolates collected from other cucurbit host types. All isolates tested were found to be sensitive to ethaboxam and EC50 values ranged from 0.18 to 3.08 mg a.i./liter with a median of 1.55 mg a.i./liter. The ratio of EC50 values for the least sensitive and the most sensitive isolate was 17.1, indicating that P. cubensis isolates were highly sensitive to ethaboxam. The most sensitive isolates to ethaboxam were collected from New York, North Carolina, and Ohio, while the least sensitive isolates were collected from Georgia, Michigan, and New Jersey. These results show that ethaboxam could be a viable addition to fungicide programs used to control CDM in the United States.

Cardiac Depression in Pigs after Multiple Trauma - Characterization of Posttraumatic Structural and Functional Alterations.

The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1ß generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.