Protein repelling coatings based on stimuli-responsive aqueous microgels decorated with oligo ethylene glycols

In the present work novel, biocompatible, thermo-responsive microgels were synthesized by surfactant-free precipitation copolymerization of N-vinylcaprolactam (VCL) with 2-methoxyethyl acrylate (MEA). MEA was chosen as comonomer because its polymer is known for his excellent blood compatibility and low protein adsorption[1,2] and therefore is already in use as coating material for artificial organs.[3] Using optimized precipitation polymerization procedure we could incorporate up to 32 mol% of MEA into the PVCL-based microgels without loss of colloidal stability. The microgel composition was quantified by Raman-Spectroscopy. Both, a high resolution transverse relaxation NMR study and calorimetric measurements delivered that MEA is located mainly in the microgel shell due to its lower polymerization rate in comparison to VCL. With increasing comonomer content the swelling degree ΔRh(20°C-50°C) of the microgels decreased. This behavior can be explained by the temperature-responsivity of both monomers. While pure PVCL microgels exhibit a LCST = 31 °C,[4] linear PMEA has a very low LCST = 0-5 C°C.[5,6] It follows that with increasing MEA-content the VPTT of the microgels is shifted to lower values. Additionally, the microgel shell is already collapsed at room temperature which prevents the swelling of the PVCL-rich core. Consequently the PVCL/MEA microgels become more rigid and less temperature-sensitive with increasing MEA-content. While the particles with low MEA-content exhibit a core-shell like structure which indicates that the core is denser than the shell, the particles with high MEA-content are rigid and compact that can be approved by AFM measurements. Furthermore, the protein repellent properties of microgel films were tested. High protein repellence could be obtained for PVCL/MEA microgels, as expected (Figure 1). At last different functionalities like carboxylic acid groups or epoxy groups were integrated into the PVCL/MEA microgels by copolymerization with acrylic acid (AA) or glycidyl methacrylate (GMA). While the carboxylic acid groups lead to additional pH-dependence of the microgels that can be used for pH-triggered uptake and release mechanisms, the epoxy groups are known to react specifically with primary amines and thiols. Therefore proteins, drugs and dyes can be bound to the microgels covalently. Please click Additional Files below to see the full abstract

Comparative ergonomic evaluation of the hand-pieces of three instrument series for root planning

Introduction: Musculoskeletal disorders (MSD) are the most frequent cause of disability in the working population, exceeding accidental trauma in frequency. The risk of developing work-related upper limb disorders (WURLDs) is high among dental hygienists and the most frequently affected are elderly subjects and women. Since such disorders can have a negative effect on the working life and on the quality of life, it is of vital importance to put in place preventive measures. Aim: To make a comparative analysis of the hand-pieces of three different manual instruments used for root planning. Materials and Methods: To evaluate the physical characteristics (section, diameter, external surface, weight) of the hand-pieces of three series of instruments for root planning, twentynine dental hygienists students were videoed while working clinically. They were also interviewed using a specific questionnaire to determine subjective preferences in terms of perceived efficacy, safety, comfort and general acceptability of the hand-piece used. Results: Lightness, full-cylindrical section with larger- diameter ends, and coating with anti-slip silicone are the most appreciated characteristics of a handpiece. Conclusions: Ergonomic analyses of manual instruments are not frequent in the dental field, and the literature reports no guidelines to guide selection of the type of hand-piece of manual instruments. The data gathered may help manufacturers in designing new manual instruments, and guiding professionals in their selection

A framework for objective evaluation of privacy filters in video surveillance

Extensive adoption of video surveillance, affecting many aspects of our daily lives, alarms the public about the increasing invasion into personal privacy. To address these concerns, many tools have been proposed for protection of personal privacy in image and video. However, little is understood regarding the effectiveness of such tools and especially their impact on the underlying surveillance tasks, leading to a tradeoff between the preservation of privacy offered by these tools and the intelligibility of activities under video surveillance. In this paper, we investigate this privacy-intelligibility tradeoff objectively by proposing an objective framework for evaluation of privacy filters. We apply the proposed framework on a use case where privacy of people is protected by obscuring faces, assuming an automated video surveillance system. We used several popular privacy protection filters, such as blurring, pixelization, and masking and applied them with varying strengths to people's faces from different public datasets of video surveillance footage. Accuracy of face detection algorithm was used as a measure of intelligibility (a face should be detected to perform a surveillance task), and accuracy of face recognition algorithm as a measure of privacy (a specific person should not be identified). Under these conditions, after application of an ideal privacy protection tool, an obfuscated face would be visible as a face but would not be correctly identified by the recognition algorithm. The experiments demonstrate that, in general, an increase in strength of privacy filters under consideration leads to an increase in privacy (i.e., reduction in recognition accuracy) and to a decrease in intelligibility (i.e., reduction in detection accuracy). Masking also shows to be the most favorable filter across all tested datasets

Oral hygiene and ONJ: a review of the literature.

The importance of oral hygiene to minimise their risk of ONJ has often been emphasized in the literature.Some patients may require a change in behaviour in terms of brushing, interdental cleaning and other oral hygiene techniques, as well as other lifestyle behaviours such as diet and tobacco use. There may also be a benefit in prescribing high fluoride toothpaste for those patients with increased caries risk.Therefore, dental hygienists and dental practitioners should give personalised preventive advice to help the patient optimise their oral health, emphasising the importance of having a healthy diet and reducing sugary snacks and drinks; maintaining excellent oral hygiene; and using fluoride toothpaste and fluoride mouthwash.The aim of the present communication was to review the literature about the protocols, methods and advises about a correct home and professional oral hygiene in patients at risk for development of ONJ and in patients affected by ONJ

Bilateral ONJ in a patient affected by metastatic prostate adenocarcinoma.

We present the diagnosis and management of a case of bilateral ONJ of the mandible in a patient that had been taking zoledronic acid treatment for 7 years following a diagnosis of metastatic prostate adenocarcinoma. The patient was referred to our Division by his dental practitioner, that had performed the extraction of the left lower first molar six months before. In the first months after the extraction the patient did not reported any symptom and he started to use a mandibular removable prosthesis. About 5 months following the extraction, the patient started to complain of pain in correspondence of the left body region. He had performed a panoramic radiograph and a CT scan showing a possible initial stage of mandibular ONJ bilaterally, with a predominance in the left mandibular body in the post-extraction socket.Therefore, a curettage of the left mandibular body was decided. Postoperative course was uneventful.Twelve months later, the patient complained of pain in the right mandibular region and in correspondence of the residual right lower third molar. A panoramic radiograph confirmed the extension of mandibular right ONJ. A curettage of the right mandibular body, together with the removal of the right lower third molar, was performed, with a following uneventful postoperative course. Two years later, the patient complained of pain in the left mandibular region in correspondence of the residual left lower second premolar. A panoramic radiograph confirmed the extension of mandibular left ONJ with involvement of the root of the aforementioned premolar. A curettage of the right mandibular body, together with the removal of the left lower second premolar, was performed, with a following uneventful postoperative course. Three years later, a complete healing was obtained

Husserl’s covert critique of Kant in the sixth book of Logical Investigations

In the final book of Logical Investigations from 1901, Husserl develops a theory of knowledge based on the intentional structure of consciousness. While there is some textual evidence that Husserl considered this to entail a critique of Kantian philosophy, he did not elaborate substantially on this. This paper reconstructs the covert critique of Kant’s theory of knowledge which LI contains. With respect to Kant, I discuss three core aspects of his theory of knowledge which, as Husserl’s reflections on Kant indicate, Husserl was familiar with. These are (i) the cooperation of two faculties for the justification of beliefs; (ii) the concept of a priori structures of knowledge Kant operated with; and (iii) the delivered transcendental proof of these structures. Regarding Logical Investigations, I first briefly outline the intentional structure of consciousness as presented in the fifth book and then turn to the theory of knowledge in the sixth book. I then clarify, partially on the basis of manuscripts and lecture notes, the covert critique of the three core aspects of Kant’s theory which the sixth book contains

Pleiotropic meta-analysis of cognition, education, and schizophrenia differentiates roles of early neurodevelopmental and adult synaptic pathways

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.Peer reviewe

Association between solar insolation and a history of suicide attempts in bipolar I disorder

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.Peer reviewe