NET formation can occur independently of RIPK3 and MLKL signaling

The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor-interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3-deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently of both RIPK3 and MLKL signaling.

Gingival labial recessions and the post-treatment proclination of mandibular incisors

INTRODUCTION A prerequisite for development of gingival recession is the presence of alveolar bone dehiscence. Proclination of mandibular incisors can result in thinning of the alveolus and dehiscence formation. OBJECTIVE To assess an association between proclination of mandibular incisor and development of gingival recession. METHODS One hundred and seventeen subjects who met the following inclusion criteria were selected: 1. age 11-14 years at start of orthodontic treatment (TS), 2. bonded retainer placed immediately after treatment (T0), 3. dental casts and lateral cephalograms available pre-treatment (TS), post-treatment (T0), and 5 years post-treatment (T5), and 4. post-treatment (T0) lower incisor inclination (Inc_Incl) <95° or >100.5°. Two groups were formed: non-proclined (N = 57; mean Inc_Incl = 90.8°) and proclined (N = 60; mean Inc_Incl = 105.2°). Clinical crown heights of mandibular incisors and the presence of gingival recession sites in this region were assessed on plaster models. Fisher's exact tests, t-tests, and regression models were computed for analysis of inter-group differences. RESULTS The mean increase of clinical crown heights (from T0 to T5) of mandibular incisors ranged from 0.75 to 0.83mm in the non-proclined and proclined groups, respectively (P = 0.273). At T5, gingival recession sites were present in 12.3% and 11.7% patients from the non-proclined and proclined groups, respectively. The difference was also not significant (P = 0.851). CONCLUSIONS The proclination of mandibular incisors did not increase a risk of development of gingival recession during five-year observation in comparison non-proclined teeth.

Reporting quality of randomised controlled trials published in prosthodontic and implantology journals

The purpose of this study was to examine the reporting quality of randomised controlled trials (RCTs) published in prosthodontic and implantology journals. Thirty issues of nine journals in prosthodontics and implant dentistry were searched for RCTs, covering the years 2005-2012: The Journal of Prosthetic Dentistry, Journal of Oral Rehabilitation, The International Journal of Prosthodontics, The International Journal of Periodontics & Restorative Dentistry, Clinical Oral Implants Research, Clinical Implant Dentistry & Related Research, The International Journal of Oral & Maxillofacial Implants, Implant Dentistry and Journal of Dentistry. The reporting quality was assessed using a modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. Data were analysed using descriptive statistics followed by univariable and multivariable examination of statistical associations (α = 0·05). A total of 147 RCTs were identified with a mean CONSORT score of 69·4 (s.d. = 9·7). Significant differences were found among journals with the Journal of Oral Rehabilitation achieving the highest score (80·6, s.d. = 5·5) followed by Clinical Oral Implants Research (73·7, s.d. = 8·3). Involvement of a statistician/methodologist was significantly associated with increased CONSORT scores. Overall, the reporting quality of RCTs in major prosthodontic and implantology journals requires improvement. This is of paramount importance considering that optimal reporting of RCTs is an important prerequisite for clinical decision-making.

Evaluation of the Morphological Characteristics of Laser-Irradiated Dentin

OBJECTIVE The aim of this study was to investigate the effect of different energy settings of Er:YAG laser irradiation on dentin surface morphology with respect to the number of opened dentinal tubules. BACKGROUND DATA An ideally prepared dentin surface with opened dentinal tubules is a prerequisite for adhesive fixation. No study, however, has yet compared the numbers of opened dentinal tubules with regard to statistical differences. METHODS Conventional preparations using a bur with or without additional acid etching acted as control groups. Dentin specimens were prepared from human third molars and randomly divided into eight groups according to the energy settings of the laser (1, 1.5, 4, 6, 7.5, and 8 W) and two controls (bur and bur plus acid etching). After surface preparation, dentin surfaces were analyzed with a scanning electron microscope, and the number of opened dentinal tubules in a defined area was counted. RESULTS The control groups showed smooth surfaces with (bur plus acid etching) and without opened dentinal tubules (bur), whereas all laser-irradiated surfaces showed rough surfaces. Using the energy setting of 4 W resulted in significantly more opened dentinal tubules than the conventional preparation technique using the bur with additional acid etching. In contrast, the energy setting of 8 W showed significantly fewer opened dentinal tubules, and also exhibited signs of thermal damage. CONCLUSIONS The Er:YAG laser with an energy setting of 4 W generates a dentin surface with opened dentinal tubules, a prerequisite for adhesive fixation.

A synthetic histone pre-mRNA-U7 small nuclear RNA chimera undergoing cis cleavage in the cytoplasm of Xenopus oocytes.

The 3' processing of histone pre-mRNAs is a nuclear event in which the U7 small nuclear ribonucleoprotein (snRNP) participates as an essential trans-acting factor. We have constructed a chimeric histone-U7 RNA that when injected into the cytoplasm of Xenopus laevis oocytes assembles into a snRNP-like particle and becomes cleaved at the correct site(s). RNP assembly is a prerequisite for cleavage, but, since neither the RNA nor the RNP appreciably enter the nucleus, cleavage occurs mostly, if not exclusively, in the cytoplasm. Consistent with this, cleavage also occurs in enucleated oocytes or in oocytes which have been depleted of U7 snRNPs. Thus all necessary components for cleavage must be present in the oocyte cytoplasm. The novel cleavage occurs in cis, involving only a single molecule of chimeric RNA with its associated proteins. This reaction is equally dependent upon base pairing interactions between histone spacer sequences and the 5'-end of the U7 moiety as the natural in trans reaction. These results imply that U7 is the only snRNP required for histone RNA processing. Moreover, the chimeric RNA is expected to be useful for further studies of the cleavage and assembly mechanisms of U7 snRNP.

Supramolecular Organization of Dye Molecules in Zeolite L Channels: Synthesis, Properties, and Composite Materials

Sequential insertion of different dyes into the 1D channels of zeolite L (ZL) leads to supramolecular sandwich structures and allows the formation of sophisticated antenna composites for light harvesting, transport, and trapping. The synthesis and properties of dye molecules, host materials, composites, and composites embedded in polymer matrices, including two- and three-color antenna systems, are described. Perylene diimide (PDI) dyes are an important class of chromophores and are of great interest for the synthesis of artificial antenna systems. They are especially well suited to advancing our understanding of the structure–transport relationship in ZL because their core fits tightly through the 12-ring channel opening. The substituents at both ends of the PDIs can be varied to a large extent without influencing their electronic absorption and fluorescence spectra. The intercalation/insertion of 17 PDIs, 2 terrylenes, and 1 quaterrylene into ZL are compared and their interactions with the inner surface of the ZL nanochannels discussed. ZL crystals of about 500 nm in size have been used because they meet the criteria that must be respected for the preparation of antenna composites for light harvesting, transport, and trapping. The photostability of dyes is considerably improved by inserting them into the ZL channels because the guests are protected by being confined. Plugging the channel entrances, so that the guests cannot escape into the environment is a prerequisite for achieving long-term stability of composites embedded in an organic matrix. Successful methods to achieve this goal are described. Finally, the embedding of dye–ZL composites in polymer matrices, while maintaining optical transparency, is reported. These results facilitate the rational design of advanced dye–zeolite composite materials and provide powerful tools for further developing and understanding artificial antenna systems, which are among the most fascinating subjects of current photochemistry and photophysics.

Management of Home Parenteral Nutrition: A Prospective Multicenter Observational Study

BACKGROUND There are no specific Swiss home parenteral nutrition (HPN) data showing patient characteristics, quality of life (QoL) and complications. The goal of this study was to collect representative nationwide data on current adult HPN patients in Switzerland for international comparability and benchmarking. METHODS This was a multicenter, nationwide, observational study. We conducted interviews for demographics, PN characteristics, QoL and complications. The data were assessed at baseline and after a follow-up of 3 months using a questionnaire. RESULTS Thirty-three adult patients were included. The most common underlying diseases were cancer, radiation enteritis and state after bariatric surgery, and the most prevalent indication was short bowel syndrome. During the 3-month observation period, significant increase or stabilization of body weight occurred in the patients, physical activity scores improved from 34.0 to 39.4 and mental scores improved from 41.9 to 46.4. HPN dependency and traveling restrictions were of the greatest concern. Diarrhea, xerostomia and/or thirst were frequent complaints. CONCLUSION Anthropometric parameters and QoL improved during the observational period in this HPN cohort. These Swiss HPN data are prerequisite for evaluation and comparison of HPN recommendations and best clinical practice, status of professional care instructions related to HPN effectiveness, quality of treatment and patient safety.

The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system.

STUDY QUESTION How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? SUMMARY ANSWER The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. WHAT IS KNOWN ALREADY Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. STUDY DESIGN, SIZE AND DURATION The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. MAIN RESULTS AND THE ROLE OF CHANCE The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs and/or segments of Müllerian ducts (complex anomaly) were involved in 27 (69.2%) types. Uterus was the organ most frequently involved (30/39: 76.9%), followed by cervix (26/39: 66.7%) and vagina (23/39: 59%). In all 39 types, the ESHRE/ESGE classification system provided a comprehensive description of each single or complex anomaly. A precise categorization was reached in 38 out of 39 types studied. Only one case of a bizarre uterine anomaly, with no clear embryological defect, could not be categorized and thus was placed in Class 6 (un-classified) of the ESHRE/ESGE system. LIMITATIONS, REASONS FOR CAUTION The review of the literature was thorough but we cannot rule out the possibility that other defects exist which will also require testing in the new ESHRE/ESGE system. These anomalies, however, must be rare. WIDER IMPLICATIONS OF THE FINDINGS The comprehensiveness of the ESHRE/ESGE classification adds objective scientific validity to its use. This may, therefore, promote its further dissemination and acceptance, which will have a positive outcome in clinical care and research. STUDY FUNDING/COMPETING INTERESTS None.

Masticatory function and nutrition in old age

Nowadays, many people retain their natural teeth until late in life as a result of the large success of preventive strategies. However, there is still a very high prevalence of edentulism especially in elderly patients and many of these patients are provided with inadequate dental prostheses. In addition, many elderly citizens suffer from systemic diseases leading to increased drug prescription with age. This may have direct or indirect negative effects on the health and integrity of oral tissues like teeth, mucosa or muscles. There is growing evidence that a close interaction between the general medical condition and oral health exists. From a dental point of view, the chewing ability and capacity and its interaction with the nutritional status seem to be especially important. For example, complete denture wearers present a significant oral disability, which often leads to a gradual deterioration of their individual dietary habits. The improvement of maximum bite force and chewing efficiency may be an important prerequisite for an adequate nutrition. Those functional parameters can often be improved by providing functional dental prostheses or by stabilizing complete dentures with endosseous implants. Nevertheless, an improvement of the nutritional status can only be achieved through a close collaboration with dieticians or clinical nutritionists.

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. This article is protected by copyright. All rights reserved.

Linguista sum... sed lingua non definio. Absence de définition de la langue et circularité de la construction structurale

This article analyzes the Jakobsonian classification of aphasias. It aims to show on the one hand the non-linguistic character of this classification and on the other hand its asymmetry, in spite of the fact that its author had conceived his structural construction as symmetrical. The non-linguistic character of Jakobson’s formulation is due to the absence of any definition of language, this absence being the main characteristic of Jakobsonian linguistics: concerning the aphasia problem, the Jakobsonian formulation is linguistic solely by virtue of its object, aphasia, which is already considered as a linguistic concern because it belongs to the field of « language », but which is not defined as such (as linguistic). As for asymmetry, it demonstrates first the circularity of the Jakobsonian representation of language (the duality between structure and functioning), and secondly the non-linguistic character – in the Saussurean sense of the term – of the aphasia problem. Thus it appears that breaking (in the sense of Gaston Bachelard) with idiom is the prerequisite of a scientific apprehension of language, and therefore of any interdisciplinarity, this being one of Jakobson’s favorite topics but one that this linguist failed to render fruitful because he did not offer a real definition of language.

The "Profiles" document: a modern revision of the objectives of undergraduate medical studies in Switzerland

The Joint Commission of the Swiss Medical Schools (SMIFK/CIMS) decided in 2000 to establish a Swiss Catalogue of Learning Objectives (SCLO) for undergraduate medical training, which was adapted from a similar Dutch blueprint. A second version of the SCLO was developed and launched in 2008. The catalogue is a prerequisite for the accreditation of the curricula of the six Swiss medical faculties and defines the contents of the Federal Licensing Examination (FLE). Given the evolution of the field of medicine and of medical education, the SMIFK/CIMS has decided to embark on a total revision of the SCLO. This article presents the proposed structure and content of Profiles, a new document which, in the future, will direct the format of undergraduate studies and of the FLE. Profiles stands for the Principal Relevant Objectives for Integrative Learning and Education in Switzerland. It is currently being developed by a group of experts from the six Swiss faculties as well as representatives of other institutions involved in these developments. The foundations of Profiles are grounded in the evolution of medical practice and of public health and are based on up-to-date teaching concepts, such as EPAs (entrustable professional activities). An introduction will cover the concepts and a tutorial will be displayed. Three main chapters will provide a description of the seven 2015 CanMEDS roles, a list of core EPAs and a series of ≈250 situations embracing the most frequent and current conditions affecting health. As Profiles is still a work in progress, it is hoped that this paper will attract the interest of all individuals involved in the training of medical students.

Proteostasis impairment in ALS.

In physiological conditions the maintenance of the cellular proteome is a prerequisite for optimal cell functioning and cell survival. Additionally, cells need to constantly sense and adapt to their changing environment and associated stressors. Cells achieve this via a set of molecular chaperones, protein clearance pathways as well as stress-associated signaling networks which work together to prevent protein misfolding, its aggregation and accumulation in subcellular compartments. These processes together form the proteostasis network which helps in maintaining cellular proteostasis. Imbalance or impairment in this processes is directly linked to ageing associated disorders such as diabetes, cancer, stroke, metabolic disorders, pulmonary fibrosis, inflammation and neurodegenerative diseases. In this review, we provide insights into the proteostasis process and how its failure governs neurodegenerative disorders with a special focus on Amyotrophic lateral sclerosis (ALS).

Assimilatory Sulfate Reduction in C3, C3-C4, and C4 Species of Flaveria

The activity of the enzymes catalyzing the first two steps of sulfate assimilation, ATP sulfurylase and adenosine 5'-phosphosulfate reductase (APR), are confined to bundle sheath cells in several C4 monocot species. With the aim to analyze the molecular basis of this distribution and to determine whether it was a prerequisite or a consequence of the C4 photosynthetic mechanism, we compared the intercellular distribution of the activity and the mRNA of APR in C3, C3-C4, C4-like, and C4 species of the dicot genusFlaveria. Measurements of APR activity, mRNA level, and protein accumulation in six Flaveria species revealed that APR activity, cysteine, and glutathione levels were significantly higher in C4-like and C4 species than in C3 and C3-C4 species. ATP sulfurylase and APR mRNA were present at comparable levels in both mesophyll and bundle sheath cells of C4 speciesFlaveria trinervia. Immunogold electron microscopy demonstrated the presence of APR protein in chloroplasts of both cell types. These findings, taken together with results from the literature, show that the localization of assimilatory sulfate reduction in the bundle sheath cells is not ubiquitous among C4 plants and therefore is neither a prerequisite nor a consequence of C4photosynthesis.

Does proximity to conspecific adults influence the establishment of ectomycorrhizal trees in rain forest?

Three ectomycorrhizal legume trees, Microberlinia bisulcata, Tetraberlinia bifoliolata and T. moreliana, form discrete groves in the southern part of Korup National Park, in southwest Cameroon and contribute c. 45–70% of stand basal area locally in a matrix of otherwise species-rich arbuscular mycorrhizal forest. A transplant experiment was performed to assess the importance of ectomycorrhizal infection associated with proximity to parents in seedling establishment of the grove-forming species. Nonectomycorrhizal seedlings of the three species were transplanted into plots of two forest types, one of high (HEM, within-grove) and one of very low (LEM, outside the grove) abundance of all three species as adult trees. For two species (T. moreliana and M. bisulcata) there was no difference in survival over 16 months, but for the third (T. bifoliolata) survival was best in HEM forest, and correlated with the basal area of adult trees of ectomycorrhizal species. Only one species (T. moreliana) increased in biomass over the experimental period; the others declined. There was no effect of forest type on overall growth of any species, but the survivors of two (T. moreliana and M. bisulcata) had heavier stems in the HEM forest. Differences in survival and growth of transplants between the three species were in accord with the ecology of the species as inferred from the frequency distributions of adult tree size in the forest. Seedlings became infected with ectomycorrhizas in both forest types; where there was a difference in extent of infection (T. moreliana) this was not related to survival or growth; and where there was a difference in survival (T. bifoliolata) this was not related to extent of infection. These results confirm that mycorrhizal inoculum associated with conspecific adults is neither a prerequisite nor a guarantee of seedling establishment, but indicates that in some circumstances there might be benefits of being close to parents. Further research is required to unravel the complexities of ectomycorrhizal community structure in this spatially and temporally heterogeneous forest, and to clarify the extent to which the various hosts share ectomycorrhizal partners.